Case Definitions
A set of case definitions has been developed by the newborn screening community to facilitate common classifications for diagnoses across programs for a majority of the core newborn screening conditions. These definitions have been developed through an iterative process by experts in state newborn screening programs and have been piloted in newborn screening programs. The intent of consensus public health surveillance case definitions for newborn screening disorders is to allow for consistent categorization and tracking of short and long-term follow-up of identified newborns at the local, regional, and national levels.
These case definitions were last updated in April 2018 and while they remain accurate, they may not, in some cases, reflect the most up-to-date clinical and diagnostic variables given the evolving nature of diagnostic technologies and increase knowledge over time around variant classifications. The development of public health surveillance case definitions remains pending for BKT, GAMT, HMG, and MPS II. Please direct any questions to newsteps@aphl.org
Metabolic Disorder:
Organic acid condition
Beta-Ketothiolase deficiency - BKT
BKT Public Health Surveillance Case Definition algorithm in development.
Glutaric acidemia type I (GA1)
| Classification | Urine or serum organic acids | Plasma Acylcarnitines | Mutation analysis | Enzyme analysis |
|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 2 known disease causing variants in the same gene (Allele 1 – variant known to be disease causing and Allele 2 – variant known to be disease causing) | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | enzyme activity consistent with disease |
| Definite | Elevated - 3-OH Glutaric and - Glutaric | Elevated C5 - DC | Untested or unknown | Untested or unknown |
| Probable | Elevated - 3-OH Glutaric | Elevated C5 - DC | Untested or unknown | Untested or unknown |
| Probable | Elevated glutaric | Elevated C5 - DC | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 – variant of unknown significance (predicted to be pathogenic)] | Untested or unknown |
| Probable | Elevated glutaric | Elevated C5 - DC | Untested or unknown | Untested or unknown |
3-Hydroxy-3- methyglutaric aciduria - HMG
HMG Public Health Surveillance Case Definition algorithm in development.
Holocarboxylase synthetase deficiency (MCD)
| Classification | Urine organic acids | Plasma Acylcarnitines | Infant chemistries/studies | Mutation analysis | Enzyme analysis |
|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | 2 known disease causing variants in the same gene (Allele 1 – variant known to be disease causing and Allele 2 – variant known to be disease causing) | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | enzyme activity on fibroblasts or WBCs consistent with disease |
| Definite | Elevated -3OH Isovaleric and -3OH Propionic and -3methylcrotonyl glycine | elevated C3; and C5-OH | Normal biotinidase studies | Untested or unknown | Untested or unknown |
| Possible | Elevated -3OH Isovaleric and -3methylcrotonyl glycine | elevated C3; and C5-OH | Normal biotinidase studies | Untested or unknown | Untested or unknown |
| Possible | Elevated -propionyl glycine and -3methylcrotonyl glycine | elevated C3; and C5-OH | Normal biotinidase studies | Untested or unknown | Untested or unknown |
| Possible | Normal | elevated C3; and C5-OH | Normal biotinidase studies | 1 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown |
| Possible | Normal | elevated C3; and C5-OH | Normal biotinidase studies | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 – variant of unknown significance) | Untested or unknown |
Isovaleric acidemia (IVA)
| Classification | Urine organic acids | Plasma Acylcarnitines | Mutation analysis | Enzyme analysis |
|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 2 known disease causing variants in the same gene (Allele 1 - variant known to be disease causing and Allele 2 - variant known to be disease causing) | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Enzyme activity on fibroblasts or WBCs consistent with disease |
| Definite | Elevated - isovalerylglycine and - 3-OH Isovaleric | Elevated C5 | Untested or unknown | Untested or unknown |
| Definite | Elevated Isovalerylglycine | Elevated C5 | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 - variant of unknown significance (predicted to be pathogenic)] | Untested or unknown |
| Possible | Elevated Isovalerylglycine | Elevated C5 | Untested or unknown | Untested or unknown |
| Possible | Elevated Isovalerylglycine | Elevated C5 | 1 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown |
| Possible | Elevated Isovalerylglycine | Elevated C5 | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 - variant of unknown significance) | Untested or unknown |
3-Methylcrotonyl-CoA carboxylase deficiency (3-MCC)
| Classification | Urine organic acids | Plasma Acylcarnitines | Maternal Studies | Mutation analysis | Enzyme analysis |
|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | 2 known disease causing mutations in the same gene | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | 2 mutations of uncertain significance in the same gene OR Only one mutation identified OR No mutations found OR Untested OR Unknown | enzyme activity consistent with disease |
| Definite | Elevated 3-OH Isovaleric with or without elevated 3-methylcrotonyl glycine | elevated C5 -OH | Maternal deficiency tested and ruled out | 2 mutations of uncertain significance in the same gene - predicted to be pathogenic | Untested or unknown |
| Probable | Elevated 3-OH Isovaleric with or without elevated 3-methylcrotonyl glycine | elevated C5 -OH | Maternal deficiency tested and ruled out | 2 mutations of uncertain significance in the same gene (one mutation may be of uncertain significance predicted to be pathogenic) | Untested or unknown |
| Probable | Elevated - 3-OH Isovaleric and - 3-methylcrotonyl glycine | elevated C5 -OH | Maternal deficiency tested and ruled out | Only one mutation identified OR No mutations found OR Untested OR Unknown | Untested or unknown |
| Possible | Elevated - 3-OH Isovaleric and - 3-methylcrotonyl glycine | Untested or unknown | Maternal deficiency tested and ruled out | Only one mutation identified OR No mutations found OR Untested OR Unknown | Untested or unknown |
| Possible | Untested or unknown | elevated C5 -OH | Maternal deficiency tested and ruled out | Only one mutation identified OR No mutations found OR Untested OR Unknown | Untested or unknown |
Methylmalonic acidemia (MMA)
| Classification | Urine or serum organic acids | Plasma Acylcarnitines | Maternal Studies | Infant chemistries/ studies | Mutation analysis | Enzyme analysis |
|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | 2 known disease causing variants in the same gene (Allele 1 - variant known to be disease causing and Allele 2 - variant known to be disease causing) | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | complementation studies consistent with corresponding disease |
| Definite | Elevated MMA for age | Elevated C3 | Absence of B12 deficiency | Absence of B12 deficiency and -Normal homocysteine | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 - variant of unknown significance (predicted to be pathogenic)] | Untested or unknown |
| Probable | Elevated MMA for age | Elevated C4 | Absence of B12 deficiency | Absence of B12 deficiency and -Normal homocysteine | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 - variant of unknown significance) | Untested or unknown |
| Probable | Elevated MMA for age | Elevated C5 | Absence of B12 deficiency | Absence of B12 deficiency and -Normal homocysteine | Untested or unknown | Untested or unknown |
| Probable | Elevated MMA for age | Elevated C6 | Absence of B12 deficiency | Absence of B12 deficiency and -Normal homocysteine | 1 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown |
| Probable | Elevated MMA for age | Elevated C7 | Absence of B12 deficiency | Absence of B12 deficiency and -Normal homocysteine | None found | Untested or unknown |
| Probable | Elevated MMA for age | Elevated C8 | Untested or unknown | Absence of B12 deficiency and -Normal homocysteine | N/A | Untested or unknown |
Methylmalonic acidemia with homocystinuria (Cbl C,D)
| Classification | Urine serum organic acids | Plasma Acylcarnitines | Maternal Studies | Infant chemistries/ studies | Mutation analysis | Enzyme analysis |
|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | 2 known disease causing variants in the same gene (Allele 1 - variant known to be disease causing and Allele 2 - variant known to be disease causing) | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Complementation studies consistent with corresponding disease |
| Definite | Elevated MMA for age | Elevated C3 | Absence of B12 deficiency | Absence of B12 deficiency and -Elevated homocysteine | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [ Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 - variant of unknown significance (predicted to be pathogenic)] | Untested or unknown |
| Probable | Elevated MMA for age | Elevated C3 | Absence of B12 deficiency | Absence of B12 deficiency and -Elevated homocysteine | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 - variant of unknown significance) | Untested or unknown |
| Probable | Elevated MMA for age | Elevated C3 | Absence of B12 deficiency | Absence of B12 deficiency and -Elevated homocysteine | Untested or unknown | Untested or unknown |
| Probable | Elevated MMA for age | Elevated C3 | Absence of B12 deficiency | Absence of B12 deficiency and -Elevated homocysteine | 1 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown |
| Possible | Elevated MMA for age | Elevated C3 | Absence of B12 deficiency | Absence of B12 deficiency and -Elevated homocysteine | None found | Untested or unknown |
| Possible | Elevated MMA for age | Elevated C3 | Untested or unknown | Absence of B12 deficiency and -Elevated homocysteine | N/A | Untested or unknown |
Propionic acidemia (PROP)
| Classification | Urine organic acids | Plasma Acylcarnitines | Mutation analysis |
|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 2 known disease causing variants in the same gene (Allele 1 - variant known to be disease causing and Allele 2 - variant known to be disease causing) |
| Definite | Presence of --methylcitrate and - +/-3OH propionic acid, propionyl glycine, -tiglyglycine and Absence of: -MMA and - methylcrotonyl glycine | Elevated C3 | Untested or unknown |
| Probable | Presence of -3-OH propionic and Absence of: -MMA and -methylcrotonyl glycine | Elevated C3 | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 - variant of unknown significance (predicted to be pathogenic)] |
| Possible | Presence of -3-OH propionic and Absence of: -MMA and -methylcrotonyl glycine | Elevated C3 | Untested or unknown |
| Possible | Presence of -3-OH propionic and Absence of: -MMA and -methylcrotonyl glycine | Elevated C3 | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 - variant of unknown significance) |
| Possible | Presence of -3-OH propionic and Absence of: -MMA and -methylcrotonyl glycine | Elevated C3 | 1 known disease causing variant (Allele 1 - variant known to be disease causing) |
| Possible | Absence of -MMA and -methylcrotonyl glycine | Elevated C3 | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 - variant of unknown significance) |
Metabolic Disorder:
Fatty acid oxidation disorder
Carnitine uptake defect/carnitine transport defect (CUD)
| Classification | Urine Carnitine excretion | Plasma Carnitine | Special Circumstance | Mutation analysis | Enzyme analysis |
|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | 2 known disease causing variants in the same gene (Allele 1 – variant known to be disease causing and Allele 2 – variant known to be disease causing) | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | enzyme activity consistent with disease |
| Definite | Elevated fractional excretion of free carnitine | Low free carnitine | Secondary carnitine loss ruled out | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Low free carnitine | Secondary carnitine loss ruled out | 2 variants of uncertain significance in the same gene - predicted to be pathogenic (Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 – variant of unknown significance (predicted to be pathogenic) | Untested or unknown |
| Possible | Untested or unknown | Low free carnitine | Secondary carnitine loss ruled out | 1 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown |
| Possible | Untested or unknown | Low free carnitine | Secondary carnitine loss ruled out | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 – variant of unknown significance) | Untested or unknown |
| Possible | Untested or unknown | Low free carnitine | Secondary carnitine loss ruled out | None found | Untested or unknown |
| Possible | Untested or unknown | Low free carnitine | Secondary carnitine loss ruled out | Untested or unknown | Untested or unknown |
Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
| Classification | Urine Organics or Aclyglycines | Plasma Acylcarnitines | Mutation Analysis | Functional Studies |
|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 2 known disease causing mutations in the same gene | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Functional fibroblast or Enzyme analysis consistent with MCAD |
| Definite | Elevated hexanoylglycine | Elevated: -C8 and -C8>C10 and -C8 >C6 and -C6 and -C10 | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Elevated: -C8 and -C8>C10 and -C8 >C6 and -C6 and -C10 | 2 mutations of uncertain significance in the same gene - predicted to be pathogenic | Untested or unknown |
| Probable | Untested or unknown | Elevated C8 on repeat testing | 1 known disease causing mutation and 1 mutation of uncertain significance in the same gene | Untested or unknown |
| Probable | Elevated hexanoylglycine | Elevated C8 on repeat testing | 1 known disease causing mutation | Untested or unknown |
| Probable | Untested or unknown | Elevated C8 on repeat testing | 2 mutations of uncertain significance in the same gene | Untested or unknown |
| Possible | Elevated hexanoylglycine | Elevated C8 on repeat testing | No mutation found | Untested or unknown |
| Possible | Elevated hexanoylglycine | Untested or unknown | 2 mutations of uncertain significance in the same gene | Untested or unknown |
| Possible | Elevated Hexanoylglycine | Untested or unknown | No mutation found | Untested or unknown |
| Possible | Untested or unknown | Elevated C8 on repeat testing | No mutation found | Untested or unknown |
| Possible or Carrier | Untested or unknown | Elevated C8 | 1 known disease causing mutation | Untested or unknown |
| Possible or Carrier | Elevated Hexanoylglycine | Normal | 1 known disease causing mutation | Untested or unknown |
Trifunctional protein deficiency (TFP) - inclusive of LCHAD
| Classification | Urine Organics | Plasma Acylcarnitines | Mutation analysis | Functional Studies |
|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 2 known disease causing variants in the same gene (Allele 1 variant known to be disease causing and Allele 2 – variant known to be disease causing) | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Functional fibroblast or Enzyme analysis consistent with LCHAD or TFP |
| Definite | Untested or unknown | Elevated: -C16-OH (on more than one specimen) and -C16:1-OH and -C18-OH and -C18:1-OH | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 – variant of unknown significance (predicted to be pathogenic)] | Untested or unknown |
| Probable | Elevated -C12-OH dicarboxylic and -C10-OH dicarboxylic | Elevated: -C16-OH (on more than one specimen)and -C16:1-OH and -C18-OH and -C18:1-OH | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Elevated: -C16-OH (on more than one specimen) and -C16:1-OH and -C18-OH and -C18:1-OH | 1 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown |
| Probable | Untested or unknown | Elevated: -C16-OH (on more than one specimen) and -C16:1-OH and -C18-OH and -C18:1-OH | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 – variant of unknown significance) | Untested or unknown |
| Possible | Untested or unknown | Elevated: -C16-OH (on more than one specimen) and -C16:1-OH and -C18-OH and -C18:1-OH | No variants found | Untested or unknown |
| Possible | Untested or unknown | Elevated: -C16-OH (on more than one specimen) and -C16:1-OH and -C18-OH and -C18:1-OH | Untested or unknown | Untested or unknown |
| Possible | Elevated -C12-OH dicarboxylic and -C10-OH dicarboxylic | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | Elevated -C12-OH dicarboxylic and -C10-OH dicarboxylic | Untested or unknown | 1 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown |
| Possible | Untested or unknown | Elevated: -C16-OH (on more than one specimen) | 2 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown |
Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD)
| Classification | Plasma Acylcarnitines | Mutation analysis | Functional Studies | |
|---|---|---|---|---|
| Definite | Untested or unknown | 2 known disease causing variants in the same gene (Allele 1 – variant known to be disease causing and Allele 2 – variant known to be disease causing) | Untested or unknown | |
| Definite | Untested or unknown | Untested or unknown | Functional fibroblast or Enzyme analysis consistent with VLCAD | |
| Definite | Elevated -C14:1 (on more than one sample) and -C14:2 and -C14 | Untested or unknown | Untested or unknown | |
| Definite | Elevated -C14:1 (on more than one sample) | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 – variant of unknown significance (predicted to be pathogenic)] | Untested or unknown | |
| Probable | Elevated -C14:1 (on more than one sample) and -C14:2 | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 – variant of unknown significance) | Untested or unknown | |
| Probable | Elevated -C14:1 (on more than one sample) | 2 variants of uncertain significance in the same gene (Allele 1 - variant of unknown significance and Allele 2 – variant of unknown significance) | Untested or unknown | |
| Probable | Elevated -C14:1 (on more than one sample) and -C14:2 | 1 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown | |
| Possible | Elevated -C14:1 (on more than one sample) and -C14:3 | Untested or unknown | Untested or unknown | |
| Possible | Elevated -C14:1 (on more than one sample) and -C14:4 | No variants found | Untested or unknown | |
| Possible | Elevated -C14:1 (on more than one sample) | Untested or unknown | Untested or unknown | |
| Possible | Elevated -C14:1 (on more than one sample) | No variants found | Untested or unknown | |
| Possible | Elevated -C14:1 (on more than one sample) | 1 known disease causing variant (Allele 1 - variant known to be disease causing) | Untested or unknown |
Metabolic Disorder:
Amino acid disorder
Arginase deficiency
| Classification | Plasma amino acids | Mutation analysis | Enzyme Studies |
|---|---|---|---|
| Definite | 2 known disease causing variants in the same gene (Allele 1 - variant known to be disease causing and Allele 2 - variant known to be disease causing) | ||
| Definite | Enzyme analysis consistent with Arginase deficiency | ||
| Probable | Elevated Arginine | 1 known disease causing mutation | |
| Possible | Elevated Arginine |
Argininosuccinic aciduria (ASA)
| Classification | Plasma or urine amino acids | Mutation analysis | Enzyme Studies |
|---|---|---|---|
| Definite | Untested or unknown | 2 known disease causing mutations in the same gene | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Enzyme analysis consistent with ASA |
| Definite | Elevated -ASA and -Citrulline | Untested or unknown | Untested or unknown |
| Definite | Elevated ASA | 2 mutations of uncertain significance in the same gene - predicted to be pathogenic | Untested or unknown |
| Possible | Elevated Citrulline | 1 known disease causing mutation | Untested or unknown |
| Possible | Elevated Citrulline | 2 mutations of uncertain significance in the same gene | Untested or unknown |
Citrullinemia, type I (CIT) - exclusive of Citrin deficiency
| Classification | Plasma amino acids | Blood Ammonia Levels | Mutation analysis | Enzyme Studies |
|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 2 known disease causing mutations in the same gene | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Enzyme analysis consistent with Citrullinemia type I |
| Definite | Elevated Citrulline and Absent ASA | Untested or unknown | 2 mutations of uncertain significance in the same gene - predicted to be pathogenic | Untested or unknown |
| Definite | Elevated Citrulline and Absent ASA | Elevated | Untested or unknown | Untested or unknown |
| Probable | Elevated Citrulline and Absent ASA | Untested or unknown | 1 known disease causing mutation | Untested or unknown |
| Probable | Elevated Citrulline and Absent ASA | Untested or unknown | 2 mutations of uncertain significance in the same gene | Untested or unknown |
| Possible | Elevated Citrulline and Absent ASA | Untested or unknown | Untested or unknown | Untested or unknown |
Classic phenylketonuria (PKU) and benign hyperphenylalanemia (H-PHE)
| Classification | Plasma amino acids | Special Studies | Mutation analysis | Enzyme Studies |
|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 2 known disease causing mutations in the same gene | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Enzyme analysis consistent with PAH deficiency |
| Definite | Elevated Phe (>120umol/L on unrestricted diet) and Phe/Tyr ratio | Normal biopterin studies | Untested or unknown | Untested or unknown |
| Possible | Elevated Phe (>120umol/L on unrestricted diet) and Phe/Tyr ratio | Untested or unknown | Untested or unknown | Untested or unknown |
Cystathionine beta-synthase (CBS) deficiency (Classic Homocystinuria)
| Classification | Plasma amino acids | Mutation analysis | Enzyme Studies |
|---|---|---|---|
| Definite | Untested or unknown | 2 known disease causing mutations in the same gene | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Enzyme analysis consistent with CBS deficiency |
| Definite | Elevated -Methionine and -Homocysteine | 2 mutations of uncertain significance in the same gene - predicted to be pathogenic | Untested or unknown |
| Probable | Elevated -Methionine and -Homocysteine | 2 mutations of uncertain significance in the same gene (may include 1 mutation predicted to be pathogenic and one mutation of uncertain significance) | Untested or unknown |
| Probable | Elevated -Methionine and -Homocysteine | 1 known disease causing mutations and 1 mutation of uncertain significance in the same gene | Untested or unknown |
| Possible | Elevated -Methionine and -Homocysteine | Only one mutation identified OR No mutations found OR Untested OR Unknown Untested or unknown | Untested or unknown |
Maple syrup urine disease (MSUD)
| Classification | Plasma amino acids | Urine Organic acids | Mutation analysis | Enzyme Studies |
|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 2 known disease causing mutations in the same gene | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Any mutation results Untested or unknown | Enzyme analysis consistent with MSUD |
| Definite | Elevated Alloisoleucine and Leu, and Val, and Ileu | Untested or unknown | Any mutation results Untested or unknown | Untested or unknown |
| Definite | Elevated Alloisoleucine | Untested or unknown | 2 mutations of uncertain significance in the same gene - predicted to be pathogenic | Untested or unknown |
| Probable | Elevated Alloisoleucine | Untested or unknown | 2 mutations of uncertain significance Only one mutation identified No mutations found Untested or unknown | Untested or unknown |
| Probable | Elevated Leu and Ile and Val and Leu>Val | 2-ketoisocaproic acid and 2-OH Isovaleric and 2-ketomethyl valeric acid | 2 mutations of uncertain significance Only one mutation identified No mutations found Untested or unknown | Untested or unknown |
| Possible | Elevated Leu and Ile and Val and Leu>Val | Untested or unknown | 3 mutations of uncertain significance Only one mutation identified No mutations found Untested or unknown | Untested or unknown |
Tyrosinemia, type I (TYR I)
| Classification | Urine or Serum studies | Mutation analysis | Enzyme Studies | |
|---|---|---|---|---|
| Definite | Untested or unknown | 2 known disease causing mutations in the same gene | Untested or unknown | |
| Definite | Untested or unknown | Untested or unknown | Enzyme analysis consistent with FAH enzyme deficiency | |
| Definite | Elevated Succinylacetone | Untested or unknown | Untested or unknown | |
| Possible | Elevated tyrosine and Normal Succinylacetone | 2 mutations of uncertain significance in the same gene - predicted to be pathogenic | Untested or unknown | |
| Possible | Elevated tyrosine and Normal Succinylacetone | 1 known disease causing mutation | Untested or unknown | |
| Possible | Elevated tyrosine and Normal Succinylacetone | 2 mutations of uncertain significance in the same gene | Untested or unknown |
Endocrine Disorder
21-Hydroxylase deficiency – classical salt wasting
| Category | Serum 17-OHP - baseline or ACTH stimulated* | Urinary steroid profiling | Serum Sodium mEq/L | Plasma Renin Activity | CYP21A2 Mutation Analysis | If available - Supportive Clinical or Laboratory Evidence |
|---|---|---|---|---|---|---|
| Definite | > 10,000 | Untested or unknown | < 135 | Untested or unknown | Untested or unknown | Evidence of salt wasting (present in shock or severe failure to thrive) |
| Definite | > 10,000 | Untested or unknown | <135 | Untested or unknown | Untested or unknown | ambiguous genitalia in 46, XX |
| Definite | > 10,000 | Untested or unknown | <135 | Untested or unknown | Untested or unknown | other hormonal evidence of CAH |
| Definite | > 10,000 | Untested or unknown | Untested or unknown | Elevated for age | Untested or unknown | Evidence of salt wasting (present in shock or severe failure to thrive) |
| Definite | > 10,000 | Untested or unknown | Untested or unknown | Elevated for age | Untested or unknown | ambiguous genitalia in 46, XX |
| Definite | > 10,000 | Untested or unknown | Untested or unknown | Elevated for age | Untested or unknown | other hormonal evidence of CAH |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | two classic gene mutations or deletions in trans | Evidence of salt wasting (present in shock or severe failure to thrive) |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | two classic gene mutations or deletions in trans | ambiguous genitalia in 46, XX |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | two classic gene mutations or deletions in trans | other hormonal evidence of CAH |
| Definite | Untested or unknown | (mass spectrometry) indicative of 21-Hydroxylase Deficiency CAH | Untested or unknown | Untested or unknown | Untested or unknown | Evidence of salt wasting (present in shock or severe failure to thrive) |
| Definite | Untested or unknown | (mass spectrometry) indicative of 21-Hydroxylase Deficiency CAH | Untested or unknown | Untested or unknown | Untested or unknown | ambiguous genitalia in 46, XX |
| Definite | Untested or unknown | (mass spectrometry) indicative of 21-Hydroxylase Deficiency CAH | Untested or unknown | Untested or unknown | Untested or unknown | other hormonal evidence of CAH |
| Probable | 1,000 -10,000 | Untested or unknown | < 135 | Untested or unknown | Untested or unknown | Evidence of salt wasting (present in shock or severe failure to thrive) |
| Probable | 1,000 -10,000 | Untested or unknown | < 135 | Untested or unknown | Untested or unknown | ambiguous genitalia in 46,XX |
| Probable | 1,000 -10,000 | Untested or unknown | < 135 | Untested or unknown | Untested or unknown | other hormonal evidence of CAH |
| Probable | 1,000 -10,000 | Untested or unknown | Untested or unknown | Elevated for age | Untested or unknown | Evidence of salt wasting (present in shock or severe failure to thrive) |
| Possible | 1,000 -10,000 | Untested or unknown | Untested or unknown | Elevated for age | Untested or unknown | ambiguous genitalia in 46,XX |
| Possible | 1,000 -10,000 | Untested or unknown | Untested or unknown | Elevated for age | Untested or unknown | other hormonal evidence of CAH |
21-Hydroxylase deficiency – classical simple virilizing
| Category | Serum 17-OHP- baseline or ACTH stimulated* | Urinary Steroid profiling | Serum Sodium mEq/L | Plasma Renin Activity | CYP21A2 Mutation Analysis | If available - Supportive Clinical or Laboratory Evidence |
|---|---|---|---|---|---|---|
| Definite | >10,000 | Untested or unknown | >135 | Untested or unknown | Untested or unknown | Ambiguous genitalia in 46,XX |
| Definite | >10,000 | Untested or unknown | >135 | Untested or unknown | Untested or unknown | no evidence of salt wasting |
| Definite | >10,000 | Untested or unknown | >135 | Untested or unknown | Untested or unknown | other hormonal evidence of CAH |
| Definite | >10,000 | Untested or unknown | Untested or unknown | Normal for age | Untested or unknown | Ambiguous genitalia in 46,XX |
| Definite | >10,000 | Untested or unknown | Untested or unknown | Normal for age | Untested or unknown | no evidence of salt wasting |
| Definite | >10,000 | Untested or unknown | Untested or unknown | Normal for age | Untested or unknown | other hormonal evidence of CAH |
| Definite | Untested or unknown | (mass spectrometry) indicative of 21-Hydroxylase Deficiency CAH | >135 | Untested or unknown | Untested or unknown | Ambiguous genitalia in 46,XX |
| Definite | Untested or unknown | (mass spectrometry) indicative of 21-Hydroxylase Deficiency CAH | >135 | Untested or unknown | Untested or unknown | no evidence of salt wasting |
| Definite | Untested or unknown | (mass spectrometry) indicative of 21-Hydroxylase Deficiency CAH | >135 | Untested or unknown | Untested or unknown | other hormonal evidence of CAH |
| Definite | Untested or unknown | (mass spectrometry) indicative of 21-Hydroxylase Deficiency CAH | Untested or unknown | Normal for age | Untested or unknown | Ambiguous genitalia in 46,XX |
| Definite | Untested or unknown | (mass spectrometry) indicative of 21-Hydroxylase Deficiency CAH | Untested or unknown | Normal for age | Untested or unknown | no evidence of salt wasting |
| Definite | Untested or unknown | (mass spectrometry) indicative of 21-Hydroxylase Deficiency CAH | Untested or unknown | Normal for age | Untested or unknown | other hormonal evidence of CAH |
| Definite | Untested or unknown | Untested or unknown | >135 | Untested or unknown | two classic gene mutations or deletions in trans | Ambiguous genitalia in 46,XX |
| Definite | Untested or unknown | Untested or unknown | >135 | Untested or unknown | two classic gene mutations or deletions in trans | no evidence of salt wasting |
| Definite | Untested or unknown | Untested or unknown | >135 | Untested or unknown | two classic gene mutations or deletions in trans | other hormonal evidence of CAH |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Normal for age | two classic gene mutations or deletions in trans | Ambiguous genitalia in 46,XX |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Normal for age | two classic gene mutations or deletions in trans | no evidence of salt wasting |
| Definite | Untested or unknown | Untested or unknown | Untested or unknown | Normal for age | two classic gene mutations or deletions in trans | other hormonal evidence of CAH |
| Probable | 1,000 -10,000 | Untested or unknown | >135 | Untested or unknown | Untested or unknown | Ambiguous genitalia in 46,XX or normal genitalia in 46,XY |
| Probable | 1,000 -10,000 | Untested or unknown | Untested or unknown | Normal for age | Untested or unknown | Ambiguous genitalia in 46,XX or normal genitalia in 46,XY |
| Probable | 1,000 -10,000 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | no evidence of salt wasting |
| * The results referenced should be obtained before the initiation of therapy. |
Primary congenital hypothyroidism (CH)
| Category | Serum TSH mU/L* | Serum Total or Free T4* |
|---|---|---|
| Definite | TSH > 10 | < age established reference range |
| Probable | TSH > 10 | normal T4/total T4 |
| Probable | TSH > 10 | Untested or unknown |
| Possible** | TSH 6-10 | < age established reference range |
| Possible ** | TSH 6-10 | Normal |
| Possible ** | TSH 6-10 | Untested or unknown |
| Incomplete | Untested or unknown | Untested or unknown |
| Incomplete | Untested or unknown | < age established reference |
| * The results referenced should be obtained before the initiation of therapy. | ||
| ** Since there can be overlap in these 2 categories (possible primary or probable secondary congenital hypothyroidism) based on the laboratory values, the treating clinician should determine which category. |
Secondary congenital hypothyroidism (CH)
| Category | Serum TSH mU/L* | Serum Total or Free T4* | Other studies |
|---|---|---|---|
| Definite | TSH < 10 | < age established reference | documentation of other pituitary hormone deficiencies or midline defects |
| Probable** | TSH < 10 | < age established reference range | no other pituitary hormone deficiencies or midline defects |
| Possible | Untested or unknown | < age established reference range | Documentation of other pituitary hormone deficiencies or midline defects |
| Possible | TSH<10 | Untested or unknown | Documentation of other pituitary hormone deficiencies or midline defects |
| Incomplete | Untested or unknown | Untested or unknown | Documentation of other pituitary hormone deficiencies or midline defects |
| Incomplete | TSH<10 | Untested or unknown | no other pituitary hormone deficiencies or midline defects |
| Incomplete | Untested or unknown | < age established reference range | no other pituitary hormone deficiencies or midline defects |
| * The results referenced should be obtained before the initiation of therapy. | |||
| ** Since there can be overlap in these 2 categories (possible primary or probable secondary congenital hypothyroidism) based on the laboratory values, the treating clinician should determine which category. |
TBG or other protein binding defect
| Category | Serum TSH mU/L | Serum Free T4 | Serum Total T4 | Other studies |
|---|---|---|---|---|
| Definite | normal | Normal for age | Low for age | Low TBG |
| Definite | normal | Normal for age | Low for age | increased T3 or T4 resin uptake |
Other Disorder
Biotinidase deficiency (BIOT)
| Classification | Enzyme Levels | Mutation analysis |
|---|---|---|
| Definite- profound | Untested or unknown | 2 known profound disease causing mutations in the same gene |
| Definite- partial | Untested or unknown | 2 known hypomorphic mutations in the same gene |
| Probable Profound | <10% normal activity | Untested or unknown |
| Probable Partial | 10-30% normal activity | Untested or unknown |
Classic galactosemia (GALT)
| Classification | GALT Levels | Gal-1-P level | Urine Galactitol | Mutation analysis |
|---|---|---|---|---|
| Definite | Definite 2 known disease causing variants in the same gene (Allele 1 – variant known to be disease causing and Allele 2 – variant known to be disease causing) | |||
| Definite | Elevated | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 – variant of unknown significance (predicted to be pathogenic)] | ||
| Definite | Elevated | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 – variant of unknown significance (predicted to be pathogenic)] | ||
| Definite | Elevated | 2 variants of uncertain significance in the same gene [Allele 1 - variant of unknown significance and Allele 2 – variant of unknown significance] | ||
| Definite | Elevated | 2 variants of uncertain significance in the same gene [Allele 1 - variant of unknown significance and Allele 2 – variant of unknown significance] | ||
| Definite | Elevated | 1 known disease causing mutation and 1 mutation of uncertain significance gene (Allele 1 – variant known to be disease causing and Allele 2 – and Allele 2 – variant of unknown significance) | ||
| Definite | Elevated | 2 known disease causing mutation and 1 mutation of uncertain significance gene (Allele 1 – variant known to be disease causing and Allele 2 – and Allele 2 – variant of unknown significance) | ||
| Probable | Elevated | |||
| Probable | Elevated | |||
| Probable | 1 known disease causing mutation (Allele 1 – variant known to be disease causing) | |||
| Probable | 2 variants of uncertain significance in the same gene - predicted to be pathogenic [Allele 1 - variant of unknown significance (predicted to be pathogenic) and Allele 2 – variant of unknown significance (predicted to be pathogenic)] | |||
| Probable | <10% | 2 variants of uncertain significance in the same gene [Allele 1 - variant of unknown significance and Allele 2 – variant of unknown significance] | ||
| Possible | <10% |
Typical cystic fibrosis (CF)
| Classification | Clinical | Sweat Chloride | Non Newborn Screen Molecular | Newborn Screen Molecular | NBS Result |
|---|---|---|---|---|---|
| Definite | >=60 mmol/L (regardless of age) | Not available or not done | 2 CF disease-causing mutations | ||
| Definite | >=60 mmol/L (regardless of age) | 2 CF disease-causing mutations | Not available or not done | ||
| Definite | No valid sweat chloride result available | 2 CF disease-causing mutations | 2 CF disease-causing mutations | ||
| Definite | No known medical condition associated with false positive sweat chloride | TWO results >=60 mmol/L (regardless of age, two independent results from separate days) | Not available or not done | Not available or not done | |
| Definite | <60 mmol/L | 2 CF disease-causing mutations and 1 or both have been shown to have lower chlorides (see CFTR2) | 2 CF disease-causing mutations and 1 or both have been previously shown to have lower chlorides, (see CFTR2) | ||
| Probable | No valid sweat chloride result available | Not available or not done | 2 CF-causing mutations | ||
| Probable | No valid sweat chloride result available | 2 CF-causing mutations | Not available or not done | ||
| Probable | >=60 mmol/L (single test, regardless of age) | Not available or not done | 2 Mutations of varying clinical consequence | ||
| Probable | >=60 mmol/L (single test, regardless of age) | Not available or not done | 2 Mutations of unknown clinical significance | ||
| Probable | >=60 mmol/L (single test, regardless of age) | 2 Mutations of varying clinical consequence | Not available or not done | ||
| Probable | >=60 mmol/L (single test, regardless of age) | 2 Mutations of unknown clinical significance | Not available or not done | ||
| Probable | <60 mmol/L | 2 CF disease-causing mutations and 1 or both have been shown to have lower chlorides | Not available or not done | ||
| Probable | <60 mmol/L | Not available or not done | 2 CF-disease-causing mutations and 1 or both have been previously shown to have lower chlorides, (see CFTR2) |
Guanidinoacetate methyltransferase (GAMT) deficiency
GAMT Public Health Surveillance Case Definition algorithm in development.
SMA
| Classification | SMN1 Copy Number (Newborn Screening Molecular*) | SMN2 Copy Number (Newborn Screening Molecular*) | SMN1 Copy Number (Post-Newborn Screening Molecular) | SMN2 Copy Number (Post-Newborn Screening Molecular) | Parental Molecular Testing Family History/Parental Genetic Testing | Clinical Symptoms at the time of Presentation** | |
|---|---|---|---|---|---|---|---|
| Definite | Zero copies of SMN1 (presumed homozygous deletion/conversion) ^ | Any | Zero copies of SMN1 (presumed homozygous deletion) ^ | Any | |||
| Definite | 2 pathogenic variants | Any | 2 pathogenic variants | Any | Phasing is complete and confirms that variants are in trans or both parents are known to be carriers of the pathogenic variants identified | ||
| Definite | 2 pathogenic variants observed on two independently collected NBS specimens | Any | Unknown/ Not Done | Any | Phasing is complete and confirms that variants are in trans or both parents are known to be carriers of the pathogenic variants identified | ||
| Definite | Unknown/ Not Done/Screen Negative | Any | 2 pathogenic variants observed on 2 independently collected specimens | Any | Phasing is complete and confirms that variants are in trans or both parents are known to be carriers of the pathogenic variants identified | ||
| Definite | Zero copies of SMN1 (presumed homozygous deletion/conversion) ^ | Unknown/ Not Done | Unknown/ Not Done | Both parents are known carriers of SMN1 deletion | |||
| Definite | Unknown/ Not Done /Screen Negative | Any | Zero copies of SMN1 (presumed homozygous deletion/conversion) | Any | Both parents are known carriers of SMN1 deletion | ||
| Definite | Unknown/ Not Done /Screen Negative | Any | Zero copies of SMN1 (presumed homozygous deletion/conversion) ^ Observed on two independently collected specimens | Any | |||
| Definite | Zero copies of SMN1 (presumed homozygous deletion/conversion) ^ observed on two independently collected NBS specimens | Any | Unknown/ Not Done | ||||
| Definite | Unknown/ Not Done /Screen Negative | Any | Zero copies of SMN1 (presumed homozygous deletion/conversion) ^ | Any | Clinical Symptoms present (see list) | ||
| Probable | Zero copies of SMN1 (presumed homozygous deletion/conversion) ^ | Any | Unknown/ Not Done | Any | Clinical symptoms present (see list) | ||
| Probable | 2 pathogenic variants | Any | 2 pathogenic variants | Phasing not done or not known | Clinical symptoms present (see list) | ||
| Probable | 2 pathogenic variants observed on two independently collected NBS specimens | Any | Unknown/ Not Done | Phasing not done or not known | Clinical symptoms present (see list) | ||
| Probable | Unknown/ Not Done/Screen Negative | Any | 2 pathogenic variants observed on 2 independent collected specimens | Phasing not done or not known | Clinical symptoms present (see list) | ||
| Possible | Zero copies of SMN1 (presumed homozygous deletion/conversion) ^ | Any | Unknown/ Not Done | Unknown/ Not Done | Unknown/ Not Done | ||
| Possible | Unknown/ Not Done /Screen Negative | Any | Zero copies of SMN1 (presumed homozygous deletion/conversion) ^ | Any | Unknown/ Not Done | Unknown | |
| Possible | 2 pathogenic variants observed on two independently collected NBS specimens | Any | Unknown/ Not Done | ||||
| Possible | Unknown/ Not Done/Screen Negative | Any | 2 pathogenic variants observed on 2 independently collected specimens | ||||
| Possible | 2 pathogenic variants | Any | 2 pathogenic variants | ||||
| Possible | 2 pathogenic variants | Any | Unknown/ Not Done | Phasing not done or not known | Clinical symptoms present (see list) | ||
| Possible | Unknown/ Not Done | Any | 2 pathogenic variants | Phasing not done or not known | Clinical symptoms present (see list) | ||
| Possible | 1 pathogenic variant and 1 variant of unknown significance | Any | 1 pathogenic variant and 1 variant of unknown significance | ||||
| Possible | 1 pathogenic variant and 1 variant of unknown significance | Any | 1 pathogenic variant and 1 variant of unknown significance | Clinical symptoms present (see list) | |||
| Possible | 1 pathogenic variant and 1 variant of unknown significance | Any | 1 pathogenic variant and 1 variant of unknown significance | Phasing is complete and confirms that variants are in trans or both parents are known to be carriers of the variants identified | With or without clinical symptoms | ||
| Possible | 2 variants of unknown significance | Any | 2 variants of unknown significance | ||||
| Possible | 2 variants of unknown significance | Any | 2 variants of unknown significance | Phasing is complete and confirms that variants are in trans or both parents are known to be carriers of the variants identified | With or without clinical symptoms | ||
| Possible | Unknown/ Not Done /Screen Negative | Any | 2 variants of unknown significance | Clinical symptoms present (see list) | |||
| KEY: ^ Presumed homozygous deletion/conversion: true deletion of exon 7 (or larger) or for which there has been a gene conversion of exon 7 (or more) * Programs need to ensure specimens are valid, taking into account NICU status and inhibitor use ** Clinical symptoms include electromyography evidence of motor neuron disease, absent reflexes, fasciculations, feeding difficulty, hypotonia, respiratory difficulty, weakness |
Variant galactosemia
| Classification | GALT Levels | Gal-1-P level | Urine Galactitol | Mutation analysis | Protein phenotyping |
|---|---|---|---|---|---|
| Definite | 1 known classic galactosemia disease causing mutation and 1 known variant galactosemia mutation | ||||
| Definite- | 10%-30% | Elevated | 1 known disease causing mutation and 1 mutation of uncertain significance- predicted to be pathogenic | ||
| Definite | 10%-30% | Elevated | 1 known disease causing mutation and 1 mutation of uncertain significance- predicted to be pathogenic | ||
| Definite | 10%-30% | Elevated | phenotype consistent with variant | ||
| Definite | 10%-30% | Elevated | phenotype consistent with variant | ||
| Definite | 10%-30% | Elevated | 1 known disease causing mutation and 1 mutation of uncertain significance | ||
| Definite | 10%-30% | Elevated | 1 known disease causing mutation and 1 mutation of uncertain significance | ||
| Probable | 10%-30% | phenotype consistent with variant | |||
| Possible | 10%-30% |
Hemoglobin Disorder:
Alpha Thalassemia Disorder
C Alpha Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | FC+Barts | Untested or unknown | Known C mutation and Deletion in alpha gene | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FC+Barts | Known C mutation and Deletion in alpha gene | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known C mutation and Deletion in alpha gene | FC+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FC+Barts | FC+Barts | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FC+Barts | Untested or unknown | Untested or unknown | FC+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FC+Barts | Untested or unknown | FC+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FC+Barts | Untested or unknown | Untested or unknown | FC+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FC+Barts | Low MCV | Both carriers | Untested or unknown | Untested or unknown |
| Probable | FC+Barts | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FC+Barts | Untested or unknown | Untested or unknown | Low MCV | Both Carriers | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FC+Barts | Low MCV | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FC+Barts |
D Alpha Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | FD+Barts | Untested or unknown | Known C mutation and Deletion in alpha gene | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FD+Barts | Known C mutation and Deletion in alpha gene | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known C mutation and Deletion in alpha gene | FD + Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FD+Barts | FD+Barts | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FD+Barts | Untested or unknown | Untested or unknown | FD+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FD+Barts | Untested or unknown | FD+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FD+Barts | Low MCV | Both carriers | Untested or unknown | Untested or unknown |
| Probable | FD+Barts | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FD+Barts | Untested or unknown | Untested or unknown | Low MCV | Both Carriers | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FD+Barts | Low MCV | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FD+Barts |
3 Deletion Alpha Thalassemia (Hgb H disease)
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA-based testing | NBS Result | CBC Results | Family DNA Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | > 25% Barts by HPLC in newborn period | 3 alpha gene defects (deletions or mutations) | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 3 alpha gene defects (deletions or mutations) | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | Barts or Hgb H | Low MCV | Parents with known carriers of 2 gene deletion and 1 gene deletion or point mutation | History of SAB/miscarriage or early termination of pregnancy | Untested or unknown |
| Probable | Persistent Barts | Untested or unknown | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Persistent Barts | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Elevated Hgb H | Untested or unknown | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Elevated Hgb H | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | Nml | Untested or unknown | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Nml | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
Hgb H Constant Spring (2 alpha gene deletion (cis) plus Constant Spring point mutation (trans)
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family DNA Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Constant Spring band identified | Untested or unknown | 3 alpha gene deletions and Constant spring mutation | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Constant Spring band identified | 3 alpha gene deletions and Constant spring mutation | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 3 alpha gene deletions and Constant spring mutation | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Constant Spring band identified | Untested or unknown | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Constant Spring band identified | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | Barts or Hgb H | Low MCV | Parents with known carriers of 2 gene and 1 gene deletion and one with Constant Spring mutation | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Constant Spring band identified | Untested or unknown | Untested or unknown | Untested or unknown | Parents with known carriers of 2 gene and 1 gene deletion and one with Constant Spring mutation | Untested or unknown | Untested or unknown |
| Probable | Constant Spring band identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Parents with known carriers of 2 gene and 1 gene deletion and one with Constant Spring mutation | Untested or unknown | Untested or unknown |
| Possible | Nml | Untested or unknown | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Nml | Untested or unknown | Barts or Hgb H | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
OArab Alpha Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | FOARAB+Barts | Untested or unknown | Known OArab mutation and Deletion in alpha gene | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FOARAB+Barts | Known OArab mutation and Deletion in alpha gene | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known OArab mutation and Deletion in alpha gene | FOARAB+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FOARAB+Barts | Untested or unknown | FOARAB+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARABTraceAA2 | FOARAB+Barts | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARAB+Barts | Untested or unknown | Untested or unknown | FOARAB+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FOARAB+Barts | Low MCV | Both carriers | Untested or unknown | Untested or unknown |
| Probable | FOARAB+Barts | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FOARAB+Barts | Untested or unknown | Untested or unknown | Low MCV | Both Carriers | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FOARAB+Barts | Low MCV | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FOARAB+Barts |
S Alpha Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | FS+Barts | Untested or unknown | Homozygous S mutation and pathological gene changes found in 1-3 of the alpha genes | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FS+Barts | Homozygous S mutation and pathological gene changes found in 1-3 of the alpha genes | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Homozygous S mutation and pathological gene changes found in 1-3 of the alpha genes | FS + Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FS+Barts | FS+Barts | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FS+Barts | Untested or unknown | Untested or unknown | FS+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FS+Barts | Untested or unknown | FS+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FS+Barts x2 | Untested or unknown | Untested or unknown | FS+Barts | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FS+Barts | Low MCV | Both parents with AS & amount of S <35%; low MCH & ruled out iron deficiency | Untested or unknown | Untested or unknown |
| Probable | FS+Barts | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both parents with AS & amount of S <35%; low MCH & ruled out iron deficiency | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FS+Barts | Untested or unknown | Untested or unknown | Low MCV | Both parents with AS & amount of S <35%; low MCH & ruled out iron deficiency | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FS+Barts |
Hemoglobin Disorder:
Beta Thalassemia Disorder
Beta + Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | SBeta + THAL | FSA or FS | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FSAA2 | Untested or unknown | SBeta + THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FSA with high A2 | SBeta + THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSAA2 | FSA with high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSAA2 | Untested or unknown | Untested or unknown | FSA or FS | Untested or unknown | Both carriers (1 each of Beta + THAL and S) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSA with high A2 | Untested or unknown | FSA or FS | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSAA2 | Untested or unknown | Untested or unknown | FSA or FS | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FS | FSA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 each of Beta + THAL and S) | Untested or unknown | Untested or unknown |
| Probable | FSAA2 x2 | Untested or unknown | Untested or unknown | FSA or FS | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSA | FSA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 each of Beta + THAL and S) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSA with high A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of Beta + THAL and S) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FSA or FS | Low MCV | Both carriers (1 each of Beta + THAL and S) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | FSA | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of Beta + THAL and S) | Untested or unknown | Untested or unknown |
| Possible | FSAA2 | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of Beta + THAL and S) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FSA or FS | Low MCV | Untested or unknown | Positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FSAA2 |
Beta Thal Major
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history |
|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | Homozygous for Point Mutation | F | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 1 Point Mutation and 1 Partial Deletion | F | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 2 Partial Deletions | F | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 2 heterozygous point mutations | F | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | High A2 (higher than normal) | Untested or unknown | F | Low MCV | Both carriers | Untested or unknown |
| Probable | F or FA (smaller A than expected) | Untested or unknown | Untested or unknown | F | Low MCV | Both carriers | Untested or unknown |
| Probable | F or FA (smaller A than expected) | High A2 (higher than normal) | Untested or unknown | F | Low MCV | Untested or unknown | Untested or unknown |
| Possible | F | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers | Untested or unknown |
| Possible | Untested or unknown | High A2 (higher than normal) | Untested or unknown | Untested or unknown | Low MCV- | Both Carriers | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | F | Low MCV- | Untested or unknown | positive |
C Beta (0) Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | C Beta 0 THAL | FCA2 or FC | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FCA2 | Untested or unknown | C Beta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FC high A2 | C Beta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCA2 or FC | FC high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCA2 or FC | Untested or unknown | Untested or unknown | FCA2 or FC | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FC high A2 | Untested or unknown | FCA2 or FC | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCA2 | Untested or unknown | Untested or unknown | FCA2 or FC | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FCA2 or FC | Low MCV | Both carriers (1 each of BetaTHAL and Beta C) | Untested or unknown | Untested or unknown |
| Probable | FCA2 or FC x2 | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta C) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FC high A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta C) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FCA2 or FC | Low MCV | Untested or unknown | Positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FCA2 |
C Beta + Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | C Beta + Thal | FCA or FC | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FCAA2 | Untested or unknown | C Beta + Thal | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FCA with high A2 | C Beta + Thal | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCAA2 | FCA with high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCAA2 | Untested or unknown | Untested or unknown | FCA or FC | Untested or unknown | Both carriers (1 with Beta + thal and one for C) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FCA with high A2 | Untested or unknown | FCA or FC | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCAA2 | Untested or unknown | Untested or unknown | FCA or FC | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCA | FCA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 with Beta + thal and one for C) | Untested or unknown | Untested or unknown |
| Probable | FCAA2 x2 | Untested or unknown | Untested or unknown | FCA or FC | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCA | FCA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 with Beta + thal and one for C) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FCA with high A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 with Beta + thal and one for C) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | FCA | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 with Beta + thal and one for C) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FCA or FC | Low MCV | Both carriers (1 with Beta + thal and one for C) | Untested or unknown | Untested or unknown |
| Possible | FCAA2 | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 with Beta + thal and one for C) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FCA or FC | Low MCV | Untested or unknown | Positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FCAA2 |
D Beta (0) Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | D Beta 0 Thal | FDA2 or FD | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FDA2 | Untested or unknown | D Beta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FD high A2 | D Beta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDA2 | FD high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDA2 | Untested or unknown | Untested or unknown | FDA2 or FD | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FD high A2 | Untested or unknown | FDA2 or FD | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDA2 or FD x 2 | Untested or unknown | Untested or unknown | FDA2 or FD | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FDA2 or FD | Low MCV | Both carriers (1 each of BetaTHAL and Beta D) | Untested or unknown | Untested or unknown |
| Probable | FDA2x2 | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta D) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FD high A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta D) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FDA2 or FD | Low MCV | Untested or unknown | Positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FDA2 |
D Beta + Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | D Beta + Thal | FDA or FD | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FDAA2 | Untested or unknown | D Beta + Thal | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FDA with high A2 | D Beta + Thal | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDAA2 | FDA with high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDAA2 | Untested or unknown | Untested or unknown | FDA or FD | Untested or unknown | Both carriers (1 with Beta + Thal and one for D) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FDA with high A2 | Untested or unknown | FDA or FD | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDAA2 | Untested or unknown | Untested or unknown | FDA or FD | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FD | FDA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 with Beta + Thal and one for D) | Untested or unknown | Untested or unknown |
| Probable | FDAA2 x2 | Untested or unknown | Untested or unknown | FDA or FD | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDA | FDA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 with Beta + Thal and one for D) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FDA with high A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 with Beta + Thal and one for D) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | FDA | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 with Beta + Thal and one for D) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FDA or FD | Low MCV | Both carriers (1 with Beta + Thal and one for D) | Untested or unknown | Untested or unknown |
| Possible | FDAA2 x2 | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 with Beta + Thal and one for D) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FDA or FD | Low MCV | Untested or unknown | Positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FDAA2 x2 |
E Beta (0) Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | EBeta 0 THAL | FEA2 or FE | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FEA2 or FE | Untested or unknown | EBeta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FE high A2 | EBeta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FEA2 or FE | FE high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FEA2 or FE | Untested or unknown | Untested or unknown | FEA2 or FE | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FE high A2 | Untested or unknown | FEA2 or FE | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FE | FE high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 each of BetaTHAL and Beta S) | Untested or unknown | Untested or unknown |
| Probable | FEA2 | Untested or unknown | Untested or unknown | FEA2 or FE | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FEA2 or FE | Low MCV | Both carriers (1 each of BetaTHAL and Beta S) | Untested or unknown | Untested or unknown |
| Probable | FEA2 or FE x2 | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta S) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FE high A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta S) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FEA2 or FE | Low MCV | Untested or unknown | Positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FEA2 |
E Beta + Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | E Beta + Thal | FEA or FE | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FEAA2 | Untested or unknown | E Beta + Thal | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FEA with high A2 | E Beta + Thal | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FEAA2 | FEA with high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FEAA2 | Untested or unknown | Untested or unknown | FEA or FE | Untested or unknown | Both carriers (1 with Beta + Thal and one for E) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FEA with high A2 | Untested or unknown | FEA or FE | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FEAA2 | Untested or unknown | Untested or unknown | FEA or FE | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FE | FEA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 with Beta + Thal and one for E) | Untested or unknown | Untested or unknown |
| Probable | FEAA2x2 | Untested or unknown | Untested or unknown | FEA or FE | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FEA | FEA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 with Beta + Thal and one for E) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FEA with high A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 with Beta + Thal and one for E) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FEA or FE | Low MCV | Both carriers (1 with Beta + Thal and one for E) | Untested or unknown | Untested or unknown |
| Possible | FEAA2x2 | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 with Beta + Thal and one for E) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FEA or FE | Low MCV | Untested or unknown | Positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FEAA2x2 |
FCHPFH
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history |
|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 1 mutation With known C mutation | FC | Low MCV | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 1 deletion and known C mutation | FC | Low MCV | Untested or unknown | Untested or unknown |
| Probable | FC | FC | Untested or unknown | Untested or unknown | Low MCV | Documented carriers of HPFH and C | Untested or unknown |
| Probable | FC | Untested or unknown | Untested or unknown | FC | Low MCV | Documented carriers of HPFH and C | Untested or unknown |
| Possible | Untested or unknown | FC | Untested or unknown | FC | Low MCV | Untested or unknown | Untested or unknown |
| Possible | FC | Untested or unknown | Untested or unknown | FC | Low MCV | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FC | Low MCV | Documented carriers of HPFH and C | Untested or unknown |
| Possible | FC | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Documented carriers of HPFH and C | Untested or unknown |
| Possible | Untested or unknown | FC | Untested or unknown | Untested or unknown | Low MCV | Documented carriers of HPFH and C | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FC | Low MCV | Untested or unknown | Positive |
FEHPFH
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history |
|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 1 deletion and known E mutation | FE | Low MCV | Untested or unknown | Untested or unknown |
| Probable | FE | FE | Untested or unknown | Untested or unknown | Low MCV | Documented carriers of HPFH and E | Untested or unknown |
| Probable | FE | Untested or unknown | Untested or unknown | FE | Low MCV | Documented carriers of HPFH and E | Untested or unknown |
| Probable | Untested or unknown | FE | Untested or unknown | FE | Low MCV | Documented carriers of HPFH and E | Untested or unknown |
| Possible | FE | Untested or unknown | Untested or unknown | FE | Low MCV | Untested or unknown | Untested or unknown |
| Possible | FE | Untested or unknown | Untested or unknown | FE | Low MCV | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FE | Low MCV | Documented carriers of HPFH and E | Untested or unknown |
| Possible | FE | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Documented carriers of HPFH and E | Untested or unknown |
| Possible | Untested or unknown | FE | Untested or unknown | Untested or unknown | Low MCV | Documented carriers of HPFH and E | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FE | Low MCV | Untested or unknown | Positive |
| C and E will not have normal MCV with HPFH - do not reference MCV |
FOArabHPFH
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history |
|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 1 mutation With known OARAB mutation | FOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 1 deletion and known OARAB mutation | FOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARAB | FOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Documented carriers of HPFH and OARAB | Untested or unknown |
| Probable | FOARAB | Untested or unknown | Untested or unknown | FOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or Unknown | FOARAB | Untested or unknown | FOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARAB | Untested or unknown | Untested or unknown | FOARAB | Untested or unknown | Documented carriers of HPFH and OARAB | Untested or unknown |
| Possible | FOARAB | Untested or | Untested or unknown | FOARAB | Normal MCV | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | FOARAB | Untested or unknown | FOARAB | Normal MCV | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FOARAB | Normal MCV | Documented carriers of HPFH and OARAB | Untested or unknown |
| Possible | FOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Normal MCV | Documented carriers of HPFH and OARAB | Untested or unknown |
| Possible | Untested or unknown | FOARAB | Untested or unknown | Untested or unknown | Normal MCV | Documented carriers of HPFH and OARAB | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FOARAB | Normal MCV | Untested or unknown | Positive |
FSHPFH
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history |
|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | 1 mutation With known S mutation | FS | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 1 deletion and known S mutation | FS | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FS | FS | Untested or unknown | Untested or unknown | Untested or unknown | Documented carriers of HPFH and S | Untested or unknown |
| Possible | Untested or unknown | FS | Untested or unknown | FS | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FS | Untested or unknown | Untested or unknown | FS | Untested or unknown | Documented carriers of HPFH and S | Untested or unknown |
| Possible | FS | Untested or unknown | Untested or unknown | FS | Normal MCV | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | FS | Untested or unknown | FS | Normal MCV | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FS | Normal MCV | Documented carriers of HPFH and S | Untested or unknown |
| Possible | FS | Untested or unknown | Untested or unknown | Untested or unknown | Normal MCV | Documented carriers of HPFH and S | Untested or unknown |
| Possible | Untested or unknown | FS | Untested or unknown | Untested or unknown | Normal MCV | Documented carriers of HPFH and S | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FS | Normal MCV | Untested or unknown | Positive |
HPFH
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history |
|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | Homozygous for Point Mutation | F | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 1 Point Mutation and 1 Deletion | F | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 2 Deletions | F | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | 2 heterozygous point mutations | F | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | F | F | Untested or unknown | Untested or unknown | Untested or unknown | Both Carriers | Untested or unknown |
| Probable | F | Untested or unknown | Untested or unknown | F | Untested or unknown | Both Carriers | Untested or unknown |
| Probable | Untested or unknown | F | Untested or unknown | F | Untested or unknown | Both Carriers | Untested or unknown |
| Probable | F | Untested or unknown | Untested or unknown | F | Untested or unknown | Both Carriers | Untested or unknown |
| Possible | F | Untested or unknown | Untested or unknown | F | Normal MCV | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | F | Untested or unknown | F | Normal MCV | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | F | Normal MCV | Both carriers | Untested or unknown |
| Possible | F | Untested or unknown | Untested or unknown | Untested or unknown | Normal MCV | Both carriers | Untested or unknown |
| Possible | Untested or unknown | F | Untested or unknown | Untested or unknown | Normal MCV | Both carriers | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | F | Normal MCV | Untested or unknown | Positive |
O Arab Beta (0) Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | OArab Beta 0 THAL | FOARABA2 or FOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FOARABA2 | Untested or unknown | OArab Beta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FOARAB High A2 | OArab Beta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARABA2 | FOARAB High A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARABA2 | Untested or unknown | Untested or unknown | FOARABA2 or FOARAB | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FOARAB High A2 | Untested or unknown | FOARABA2 or FOARAB | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARABA2 x2 | Untested or unknown | Untested or unknown | FOARABA2 or FOARAB | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FOARABA2 or FOARAB | Low MCV | Both carriers (1 each of BetaTHAL and Beta O Arab) | Untested or unknown | Untested or unknown |
| Probable | FOARABA2 x2 | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta O Arab) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FOARAB High A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta O Arab) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FOARABA2 or FOARAB | Low MCV | Untested or unknown | Positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FOARABA2 |
O Arab Beta +Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | OArab Beta + THAL | FOARABA or FOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FOARABAA2 | Untested or unknown | OArab Beta + THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FOARAB A with high A2 | OArab Beta + THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARABAA2 | FOARAB A with high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARABAA2 x2 | Untested or unknown | Untested or unknown | FOARABA or FOARAB | Untested or unknown | Both carriers (1 Beta + Thal and OARAB | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FOARAB A with high A2 | Untested or unknown | FOARABA or FOARAB | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARABAA2 | Untested or unknown | Untested or unknown | FOARABA or FOARAB | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARAB | FOARABA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 Beta + Thal and OARAB | Untested or unknown | Untested or unknown |
| Probable | FOARABAA2 x2 | Untested or unknown | Untested or unknown | FOARABA or FOARAB | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FOARABA | FOARABA | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 Beta + Thal and OARAB | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FOARAB A with high A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 Beta + Thal and OARAB | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FOARABA or FOARAB | Low MCV | Both carriers (1 Beta + Thal and OARAB | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | FOARAB A | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 Beta + Thal and OARAB | Untested or unknown | Untested or unknown |
| Possible | FOARABAA2 | Untested or unknown | Untested or | Untested or | Low MCV | Both carriers (1 Beta + Thal and OARAB | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FOARABAA2 | Low MCV | Untested or unknown | Positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FOARABAA2 |
S Beta (0) Thal
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA sequencing and deletion | NBS result | CBC Results | Family Studies | Family history | HPLC & IEF same sample |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | Untested or unknown | SBeta 0 THAL | FSA2 or FS | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | FSA2 or FS | Untested or unknown | SBeta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FS high A2 | SBeta 0 THAL | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSA2 or FS | FS high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSA2 or FS | Untested or unknown | Untested or unknown | FSA2 or FS | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FS high A2 | Untested or unknown | FSA2 or FS | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FS | FS high A2 | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 each of BetaTHAL and Beta S) | Untested or unknown | Untested or unknown |
| Probable | FSA2 or FS | Untested or unknown | Untested or unknown | FSA2 or FS | Low MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FSA2 or FS | Low MCV | Both carriers (1 each of BetaTHAL and Beta S) | Untested or unknown | Untested or unknown |
| Probable | FSA2 or FS x2 | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta S) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FS high A2 | Untested or unknown | Untested or unknown | Low MCV | Both carriers (1 each of BetaTHAL and Beta S) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FSA2 or FS | Low MCV | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Low MCV | Untested or unknown | Untested or unknown | FSA2 |
Hemoglobin Disorder:
Sickle Cell Disorder
CC disease
| Category | Qualitative (IEF or HPLC) | Quantiative (HPLC or electrophoresis) | DNA | NBS result | CBC | Family Studies | Family history | Hbg testing (Electrophoresis or HPLC) on family members |
|---|---|---|---|---|---|---|---|---|
| Definite | Untested or unknown | FC | CC | Untested or unknown | Nml MCV | Both carriers C | Untested or unknown | Untested or unknown |
| Definite | FC | Untested or unknown | CC | Untested or unknown | Nml MCV | Both carriers C | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | CC | FC | Nml MCV | Both carriers C | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | CC | Untested or unknown | Untested or unknown | Both Carriers C | ||
| Probable | Untested or unknown | FC | Untested or unknown | FC | Untested or unknown | Both carriers | Untested or unknown | Untested or unknown |
| Probable | FC | FC | Untested or unknown | Untested or unknown | Untested or unknown | Both Carriers C | Untested or unknown | Untested or unknown |
| Probable | FC | Untested or unknown | Untested or unknown | FC | Untested or unknown | Both carriers | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FC | Nml MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FC | Untested or unknown | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FC | Untested or unknown | Untested or unknown | Untested or unknown | positive |
CD disease
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA | NBS result | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|
| Definite | FCD | Untested or unknown | Known C and known D mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FCD | Known C and known D mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known C and known D mutation identified | FCD | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCD | FCD | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCD | Untested or unknown | Untested or unknown | FCD | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FCD | Untested or unknown | FCD | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FCD | Both carriers (1 with D and 1 with E) | Untested or unknown | Untested or unknown |
| Probable | FCD | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 with D and 1 with E) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FCD | Untested or unknown | Untested or unknown | Both carriers (1 with D and 1 with E) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FCD | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | FCD |
CE disease
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA | NBS result | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|
| Definite | FCE | Untested or unknown | Known C and known E mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FCE | Known C and known E mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known C and known E mutation identified | FCE | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCE | FCE | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCE | Untested or unknown | Untested or unknown | FCE | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FCE | Untested or unknown | FCE | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FCE | Both carriers (1 with C and 1 with E) | Untested or unknown | Untested or unknown |
| Probable | FCE | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 with C and 1 with E) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FCE | Untested or unknown | Untested or unknown | Both carriers (1 with C and 1 with E) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FCE | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | FCE |
COArab disease
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA | NBS result | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|
| Definite | FCOARAB | Untested or unknown | Known C and known OARAB mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FCOARAB | Known C and known OARAB mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known C and known OARAB mutation identified | FCOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCOARAB | FCOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FCOARAB | Untested or unknown | Untested or unknown | FCOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FCOARAB | Untested or unknown | FCOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FCOARAB | Both carriers (1 carrier C and 1 carrier OARAB) | Untested or unknown | Untested or unknown |
| Probable | FCOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 carrier C and 1 carrier OARAB) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FCOARAB | Untested or unknown | Untested or unknown | Both carriers (1 carrier C and 1 carrier OARAB) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FCOARAB | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | FCOARAB |
DD disease
| Category | Qualitative (IEF or HPLC) | Quantiative (HPLC or electrophoresis) | DNA- | NBS result | CBC | Family Studies | Family history | Hbg testing (Electrophoresis or HPLC) on family members |
|---|---|---|---|---|---|---|---|---|
| Definite | FD | Untested or unknown | DD | Untested or unknown | Nml MCV | Both carriers D | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FD | DD | Untested or unknown | Nml MCV | Both carriers D | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | DD | FD | Nml MCV | Both carriers D | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | DD | Untested or unknown | Untested or unknown | Both Carriers D | Untested or unknown | Untested or unknown |
| Probable | FD | FD | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers D | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FD | Untested or unknown | FD | Untested or unknown | Both carriers | Untested or unknown | Untested or unknown |
| Probable | FD | Untested or unknown | Untested or unknown | FD | Untested or unknown | Both carriers | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FD | Nml MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FD | Untested or unknown | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FD | Untested or unknown | Untested or unknown | Untested or unknown | positive |
DE disease
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA | NBS result | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|
| Definite | FDE | Untested or unknown | Known D and known E mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FDE | Known D and known E mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known D and known E mutation identified | FDE | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDE | FDE | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDE | Untested or unknown | Untested or unknown | FDE | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FDE | Untested or unknown | FDE | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FDE | Both carriers (1 carrier E and 1 carrier D) | Untested or unknown | Untested or unknown |
| Probable | FDE | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 carrier E and 1 carrier D) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FDE | Untested or unknown | Untested or unknown | Both carriers (1 carrier E and 1 carrier D) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FDE | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | FDE |
DOArab disease
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA | NBS result | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|
| Definite | FDOARAB | Untested or unknown | Known OARAB and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FDOARAB | Known OARAB and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known OARAB and known S mutation identified | FDOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDOARAB | FDOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FDOARAB | Untested or unknown | Untested or unknown | FDOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FDOARAB | Untested or unknown | FDOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FDOARAB | Both carriers (1 carrier C and 1 carrier OARAB) | Untested or unknown | Untested or unknown |
| Probable | FDOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers (1 carrier C and 1 carrier OARAB) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FDOARAB | Untested or unknown | Untested or unknown | Both carriers (1 carrier C and 1 carrier OARAB) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FDOARAB | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | FDOARAB |
EE disease
| Category | Qualitative (IEF or HPLC) | Quantiative (HPLC or electrophoresis) | DNA- no deletion/duplication analysis | NBS result | CBC | Family Studies | Family history | Hbg testing (Electrophoresis or HPLC) on family members |
|---|---|---|---|---|---|---|---|---|
| Definite | FE | Untested or unknown | EE | Untested or unknown | Nml MCV | Both carriers E | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FE | EE | Untested or unknown | Nml MCV | Both carriers E | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | EE | FE | Nml MCV | Both carriers E | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | EE | Untested or unknown | Untested or unknown | Both Carriers E | Untested or unknown | Untested or unknown |
| Probable | FE | FE | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers E | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FE | Untested or unknown | FE | Untested or unknown | Both carriers | Untested or unknown | Untested or unknown |
| Probable | FE | Untested or unknown | Untested or unknown | FE | Untested or unknown | Both carriers | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FE | Nml MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FE | Untested or unknown | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FE | Untested or unknown | Untested or unknown | Untested or unknown | positive |
Homozygous OArab disease
| Category | Qualitative (IEF or HPLC) | Quantiative (HPLC or electrophoresis) | DNA- | NBS result | CBC | Family Studies | Family history | Hbg testing (Electrophoresis or HPLC) on family members |
|---|---|---|---|---|---|---|---|---|
| Definite | FOARAB | Untested or unknown | OARABOARAB | Untested or unknown | Nml MCV | Both carriers OARAB | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FOARAB | OARABOARAB | Untested or unknown | Nml MCV | Both carriers OARAB | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | OARABOARAB | FOARAB | Nml MCV | Both carriers OARAB | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | OARABOARAB | Untested or unknown | Untested or unknown | Both carriers OARAB | Untested or unknown | Untested or unknown |
| Probable | FOARAB | FOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers OARAB | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FOARAB | Untested or unknown | FOARAB | Untested or unknown | Both carriers | Untested or unknown | Untested or unknown |
| Probable | FOARAB | Untested or unknown | Untested or unknown | FOARAB | Untested or unknown | Both carriers | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FOARAB | Nml MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FOARAB | Untested or unknown | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FOARAB | Untested or unknown | Untested or unknown | Untested or unknown | positive |
SC disease
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA | NBS result | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|
| Definite | FSC | Untested or unknown | Known C and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FSC | Known C and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known C and known S mutation identified | FSC | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known C and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | FSC |
| Probable | FSC | FSC | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSC | Untested or unknown | Untested or unknown | FSC | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSC | Untested or unknown | FSC | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FSC | Both carriers ( 1 with C mutation and other with S mutation) | Untested or unknown | Untested or unknown |
| Probable | FSC | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers ( 1 with C mutation and other with S mutation) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSC | Untested or unknown | Untested or unknown | Both carriers ( 1 with C mutation and other with S mutation) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FSC | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | FSC |
SD disease
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA | NBS result | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|
| Definite | FSD | Untested or unknown | Known D and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FSD | Known D and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known D and known S mutation identified | FSD | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known D and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | FSD |
| Probable | FSD | FSD | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSD | Untested or unknown | Untested or unknown | FSD | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSD | Untested or unknown | FSD | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FSD | Both carriers ( 1 with known S mutation and 1 with known D mutation) | Untested or unknown | Untested or unknown |
| Probable | FSD | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers ( 1 with known S mutation and 1 with known D) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSD | Untested or unknown | Untested or unknown | Both carriers ( 1 with known S mutation and 1 with known D) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FSD | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | FSD |
SE disease
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA | NBS result | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|
| Definite | FSE | Untested or unknown | Known E and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FSE | Known E and known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known E and known S mutation identified | FSE | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSE | FSE | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSE | Untested or unknown | Untested or unknown | FSE | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSE | Untested or unknown | FSE | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FSE | Both carriers ( 1 with known S mutation and 1 with known E) | Untested or unknown | Untested or unknown |
| Probable | FSE | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers ( 1 with known S mutation and 1 with knownE) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSE | Untested or unknown | Untested or unknown | Both carriers ( 1 with known S mutation and 1 with known E) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FSE | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | FSE |
SOArab disease
| Category | Qualitative (IEF or HPLC) | Quantitative (HPLC or electrophoresis) | DNA | NBS result | Family Studies | Family history | HPLC& IEF same sample |
|---|---|---|---|---|---|---|---|
| Definite | FSOARAB | Untested or unknown | Known OARABand known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FSOARAB | Known OARABand known S mutation identified | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | Known OARABand known S mutation identified | FSOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSOARAB | FSOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | FSOARAB | Untested or unknown | Untested or unknown | FSOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSOARAB | Untested or unknown | FSOARAB | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | Untested or unknown | FSOARAB | Both carriers ( 1 with known S mutation and 1 with known OARAB) | Untested or unknown | Untested or unknown |
| Probable | FSOARAB | Untested or unknown | Untested or unknown | Untested or unknown | Both carriers ( 1 with known S mutation and 1 with known OARAB) | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FSOARAB | Untested or unknown | Untested or unknown | Both carriers ( 1 with known S mutation and 1 with known OARAB) | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FSOARAB | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | Untested or unknown | FSOARAB |
SS disease (Sickle cell anemia)
| Category | Qualitative (IEF or HPLC) | Quantiative (HPLC or electrophoresis) | DNA- | NBS result | CBC | Family Studies | Family history | Hbg testing (Electrophoresis or HPLC) on family members |
|---|---|---|---|---|---|---|---|---|
| Definite | FS | Untested or unknown | SS | Untested or unknown | Untested or unknown | Both carriers S | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | FS | SS | Untested or unknown | Untested or unknown | Both carriers S | Untested or unknown | Untested or unknown |
| Definite | Untested or unknown | Untested or unknown | SS | FS | Untested or unknown | Both carriers S | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | Untested or unknown | SS | Untested or unknown | Untested or unknown | Both carriers S | ||
| Probable | FS | Untested or unknown | Untested or unknown | FS | Nml- high MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Probable | Untested or unknown | FS | Untested or unknown | FS | Untested or unknown | Both carriers S | Untested or unknown | Untested or unknown |
| Probable | FS | Untested or unknown | Untested or unknown | FS | Untested or unknown | Both carriers S | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FS | Nml- high MCV | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FS | Untested or unknown | Untested or unknown | positive | Untested or unknown |
| Possible | Untested or unknown | Untested or unknown | Untested or unknown | FS | Untested or unknown | Untested or unknown | Untested or unknown | positive |
Lysosomal Storage Disorder
Mucopolysaccharidosis I (MPS I)
| Classification | Disorder | Mutation Status | Enzyme Activity | Urine GAGS | Clinical Symptoms/ Lab Findings |
|---|---|---|---|---|---|
| Definite | MPS I - severe | Allele 1 - pathogenic* and associated with severe disease and Allele 2 - pathogenic and associated with severe disease # | Within lab known affected range | Elevated | |
| Definite | MPS I - severity not determined | Allele 1 - pathogenic* or likely pathogenic and Allele 2 - variant with uncertain significance | Within lab known affected range | Elevated | |
| Definite | MPS I - severity not determined | Unknown/Not Done | Within lab known affected range | Elevated | |
| Probable | MPS I - severe | Allele 1 - pathogenic* and associated with severe disease and Allele 2 - pathogenic* and associated with severe disease # | Within lab known affected range | Unknown/Not Done | |
| Probable | MPS I - severe | Allele 1 - pathogenic* and associated with severe disease and Allele 2 - pathogenic* and associated with severe disease # | Unknown | Unknown/Not Done | |
| Definite | MPS I Attenuated | Allele 1 - pathogenic* and associated with severe disease and Allele 2 - variant known to be associated with ATTENUATED Disease # | Within lab known affected range | Elevated | Symptoms present and documented by specialists. PH program continued to collect data through the development of symptoms** |
| Definite | MPS I Attenuated | Allele 1 - variant known to be associated with ATTENUATED Disease and Allele 2 - variant known to be associated with ATTENUATED Disease # | Within lab known affected range | Elevated | |
| Probable | MPS I Attenuated | Allele 1 - pathogenic* and associated with severe disease and Allele 2 - variant known to be associated with ATTENUATED Disease # | Unknown/Not Done | Unknown/Not Done | Symptoms present and documented by specialists. PH program continued to collect data through the development of symptoms** |
| Possible | MPS I Attenuated | Allele 1 - pathogenic* and associated with severe disease and Allele 2 - variant known to be associated with ATTENUATED Disease # | Within lab known affected range | Unknown/Not Done | Unknown |
| Possible | MPS I Attenuated | Allele 1 - pathogenic* and associated with severe disease and Allele 2 - variant known to be associated with ATTENUATED Disease # | Unknown | Unknown/Not Done | |
| Possible | MPS I - severity not determined | Allele 1 - pathogenic* and associated with severe disease and Allele 2 - variant of unknown significance | Unknown | Unknown/Not Done | Symptoms present and documented by specialists. PH program continued to collect data through the development of symptoms** |
| Possible | MPS I Attenuated | Allele 1 - pathogenic* and associated with severe disease and Allele 2 - variant of unknown significance | Unknown | Unknown/Not Done | No symptoms by the time the PH Program closes follow-up (either due to child being lost to follow-up OR program policy on follow-up time |
| *Pathogenic: Reported in cases known to have severe cases previously. | |||||
| # All reports of two variants determined to be disease causing are assumed to bin in trans, and appropriate testing was completed as necessary | |||||
| ** Clinical symptoms consistent with MPS I include: Hepatosplenomegaly, Coarse facial features, Hydrocephalus, Skeletal deformities (dysostosis multiplex), Corneal clouding, Large tongue, Prominent forehead, Joint stiffness, Short stature, frequent ear infections and hearing loss, hernia |
Mucopolysaccharidosis II (MPS II)
MPS II Public Health Surveillance Case Definition algorithm in development.
Pompe Disease
| Classification | Disorder | Mutation Status | Blood (not DBS sample) | Skin/Muscle testing | Cardiac Involvement consistent with Pompe | Lab Findings | Clinical Findings |
|---|---|---|---|---|---|---|---|
| Definite | Infantile Onset Pompe Disease | Allele 1 - pathogenic and associated with infantile onset and Allele 2 - pathogenic and associated with infantile onset | Within lab known affected range for infantile onset (IO) | Not done or positive skin or muscle bx | Positive findings on Chest X-ray/EKG/ECHO in newborn period | Unknown/ Not Done | |
| Definite | Infantile Onset Pompe Disease | Unknown or not done | Within lab known affected range for IO | Not done or positive skin or muscle bx | Positive findings on Chest X-ray/EKG/ECHO in newborn period | Elevated CK/AST/ALT/LDH/Urine Hex4 | |
| Definite | Infantile Onset Pompe Disease | Allele 1 - pathogenic and associated with infantile onset, 1 novel variant that is likely pathogenic | Within lab known affected range for IO | Not done or positive skin or muscle bx | Positive findings on Chest X-ray/EKG/ECHO in newborn period | Elevated CK/AST/ALT/LDH/Urine Hex4 | |
| Definite | Infantile Onset Pompe Disease | Allele 1 - pathogenic and associated with infantile onset and Allele 2 - pathogenic and associated with infantile onset | Within lab known affected range for IO | Not done or positive skin or muscle bx | Positive findings on Chest X-ray/EKG/ECHO in newborn period | Elevated CK/AST/ALT/LDH/Urine Hex4 | |
| Definite | Infantile Onset Pompe Disease | 1 pathogenic* or likely pathogenic variant, with deletion or duplication consistent with infantile onset | Within lab known affected range for IO | Not done | Positive findings on Chest X-ray/EKG/ECHO in newborn period | Elevated CK/AST/ALT/LDH/Urine Hex4 | |
| Definite | Infantile Onset Pompe Disease | Allele 1 - pathogenic and associated with infantile onset and Allele 2 - pathogenic and associated with non-classical disease, or variant of uncertain significance | Low (above affected range, for IO, may or may not be in late-onset (LO) range but should not be above LO range) | Positive skin or muscle bx | Positive findings on Chest X-ray/EKG/ECHO in newborn period | Elevated CK/AST/ALT/LDH/Urine Hex4 | |
| Probable | Infantile Onset Pompe Disease | Allele 1 - pathogenic and associated with infantile onset and Allele 2 - pathogenic and associated with non-classical disease, or variant of uncertain significance | Within lab known affected range for IO | Unknown/ not done | Positive findings on Chest X-ray/EKG/ECHO | Unknown/ Not Done | |
| Probable | Infantile Onset Pompe Disease | 1 pathogenic* or likely pathogenic variant, no other variants found, dup/del testing not done or not known | Within lab known affected range for IO | Unknown/ not done | Positive findings on Chest X-ray/EKG/ECHO | Elevated CK/AST/ALT/LDH/Urine Hex4 | |
| Definite | Late Onset Pompe disease | Allele 1 - pathogenic and Allele 2 - pathogenic and associated with non-classical disease, or variant of uncertain significance | Within lab known affected range for LO | Unknown/ not done | No | Elevated CK/AST/ALT/LDH/Urine Hex4 | Symptoms present after 1 year of age and documented by specialists. PH program continued to collect data through the development of symptoms** |
| Definite | Late Onset Pompe disease | Allele 1 - pathogenic and Allele 2 - pathogenic and associated with non-classical disease, or variant of uncertain significance | Within lab known affected range for LO | Unknown/ not done | No | Elevated CK/AST/ALT/LDH/Urine Hex4 | Symptoms present before 1 year of age but no cardiac involvement |
| Probable | Late Onset Pompe disease | Allele 1 - pathogenic and Allele 2 - pathogenic and associated with non-classical disease, or variant of uncertain significance | Within lab known affected range for LO | Unknown/ not done | No | Elevated CK/AST/ALT/LDH/Urine Hex4 | Unknown or not reported to PH to program by the end of follow-up |
| Possible | Late Onset Pompe disease | Allele 1 - pathogenic* and associated with infantile onset and Allele 2 - pathogenic* | Low (above affected range, for LO not normal) | Unknown/ not done | No | Not present | |
| Possible | Late Onset Pompe disease | Allele 1 - pathogenic* and associated with infantile onset, no other variants detected; Duplication/deletion testing not completed or unknown | Within lab known affected range for LO | Unknown/ not done | No | Not present | |
| Definite | Late Onset Pompe disease | Allele 1 - pathogenic* and associated with infantile onset, no other variants detected; Duplication/deletion testing not completed or unknown | Within lab known affected range for LO | Unknown/ not done | No | Elevated CK/AST/ALT/LDH/Urine Hex4 | Symptoms present after 1 year of age and documented by specialists. PH program continued to collect data through the development of symptoms** |
| Possible | Late Onset Pompe disease | 1 pathogenic* or likely pathogenic variant, no other variants found | Within lab known affected range | Unknown/ not done | No | Elevated CK/AST/ALT/LDH/Urine Hex4 | |
| Possible | Late Onset Pompe disease | 2 pathogenic* or likely pathogenic variant, no other variants found | Within lab known affected range | Unknown/ not done | No | Not present | |
| *Pathogenic: classified as pathogenic or likely pathogenic by ACMG Guidelines (2015) | |||||||
| ** Clinical symptoms consistent with Pompe Disease: progressive muscle weakness, need for respiratory assistance, swaying gait or waddle, Lordosis, kyphosis, or scoliosis |
SCID
Leaky SCID
| Classification: | CD3 T cells/ μl | Proliferation | Maternal engraftment Y/N | Molecular testing | Clinical Presentation |
|---|---|---|---|---|---|
| Definite | 300-1500, few naive T cells, oligoclonal T cells or poor T cell diversity | 10-50% normal PHA | No | Unknown or not done | |
| Definite | 300-1500, few naive T cells | 10-50% normal PHA | No | Consistent with SCID^ | |
| Possible | 300-1500, few naive T cells | Unknown or any | No | Unknown or not done | |
| Definite | 300-1500, few naive T cells | Unknown or any | No | Consistent with SCID^ | |
| Possible | Any number | 10-30% normal PHA or Absent to Candida/TT | No | Unknown or not done | |
| Definite | Any number | 10-30% normal PHA or Absent to Candida/TT | No | Consistent with SCID^ | |
| ^ Consistent with Leaky SCID: Two pathogenic variants in a known SCID gene known to be associated with leaky SCID (previously reported or in a gene previously associated with a combined immune deficiency ) or one pathogenic variant in SCID gene on X chromosome in a male; ruled out 22q11 deletion; ruled out heterozygous TBX1 variants; ruled out homozygous or compound heterozygous FOXN1 mutations |
Non-SCID conditions associated with SCID NBS
| Classification | Findings |
|---|---|
| Syndromes with low T-cell numbers | Recognized genetic syndrome that includes variable immune defects, with some cases having significantly low T-cell numbers (DiGeorge syndrome, FOXN1, CHARGE syndrome, Trisomy 21, Jacobsen syndrome, RAC2 defect, DOCK8 deficiency, Ataxia Telangiectasia, VACTERL association, Barth syndrome, TAR syndrome, Ectrodactyly Ectodermal Dysplasia syndrome, Cartilage Hair Hypoplasia, others) |
| Secondary T-cell lymphopenia | Congenital malformation or disease process without an intrinsic defect in production of circulating T-cells (e.g. congenital heart disease with vascular leak, hydrops, gastroschisis, chylothorax, intestinal lymphangiectasia, others) |
| Preterm birth alone | Preterm birth and low birth weight, with low T cell numbers early in life that normalize over time |
| Idiopathic T-cell lymphopenia (formerly called Variant SCID) | Persistently low T cell numbers for over 3 months without recognized cause |
| In all of these other conditions there is 1) no maternal engraftment, 2) the T cells are largely naive, 3) PHA proliferation is usually normal. |
Omenn Syndrome
| Classification: | CD3 T cells/ μl | Proliferation to PHA | Maternal engraftment Y/N | Molecular testing | Clinical Presentation |
|---|---|---|---|---|---|
| Definite | >80%CD45RO+ | 10-50%normal | No | Consistent with OS/SCID^^ | Consistent with OS** |
| Definite | >80%CD45RO+ | 10-50%normal | No | Untested or unknown | Consistent with OS** |
| Definite | >80%CD45RO+ | 10-50%normal | No | No variant reported, ruled out 22q11 and FOXN1 | Consistent with OS** |
| Probable | >80%CD45RO+ | Untested or unknown | No | Consistent with OS/SCID^^ | Consistent with OS** |
| Probable | >80%CD45RO+ | 10-50%normal | Unknown | Untested or unknown | Consistent with OS** |
| Uncertain | >80%CD45RO+ | Untested or unknown | Untested or Unknown | Untested or unknown | Consistent with OS** |
| ** Clinical presentation may include Erythroderma with biopsy showing T cell infiltrate; hepatomegaly, splenomegaly or both; adenopathy, eosinophilia, elevated levels of serum IgE antibody | |||||
| ^^ Consistent with OS/SCID: Two pathogenic variants in a SCID gene known to be associated with leaky SCID (previously reported or in a gene previously associated with a combined immune deficiency) or one pathogenic variant in SCID gene on X chromosome in a male; ruled out 22q11 deletion; ruled out heterozygous TBX1 variants; ruled out homozygous or compound heterozygous FOXN1 mutations |
Typical SCID
| Classification: | CD3 T cells/ μl | Proliferation to PHA | Maternal engraftment Y/N | Molecular testing | Clinical Presentation |
|---|---|---|---|---|---|
| Definite | <300 autologous T Cells, undetectable or very few naive T cells | <10% of normal | Yes | Consistent with SCID^ | |
| Definite | <300 autologous T Cells, undetectable or very few naive T cells | <10% of normal | Yes | Unknown or not done | |
| Definite | <300 autologous T Cells, undetectable or very few naive T cells | Unknown or any | Yes | Consistent with SCID^ | |
| Definite | Any number | <10% of normal | Yes | Consistent with SCID^ | |
| Definite | <300 autologous T Cells, undetectable or very few naive T cells | <10% of normal | No | Consistent with SCID^ | |
| Probable | <300 autologous T Cells, undetectable or very few naive T cells | <10% of normal | No | Unknown or not done | |
| Probable | Any number | <10% of normal | No | Consistent with SCID^ | |
| Probable | Any number | <10% of normal | Yes | Unknown or not done | |
| Probable | Any number | Unknown or any | Yes | None or inconclusive | |
| Probable | Any number | Unknown or any | Yes | Consistent with SCID^ | |
| Possible | <300 autologous T Cells, undetectable or very few naive T cells | <10% of normal | Untested or unknown | Untested or unknown | Untested or unknown |
| Possible | <300 autologous T Cells, undetectable or very few naive T cells | Unknown or any | No | Unknown or not done | |
| Possible | <300 autologous T Cells, undetectable or very few naive T cells | Unknown or any | No | Consistent with SCID^ | |
| Probable | <300 autologous T Cells, undetectable or very few naive T cells | Unknown or any | Yes | Unknown or not done | |
| Possible | Any number | Unknown or any | No | Consistent with SCID^ | |
| Possible | Any number | <10% of normal | No | None or inconclusive | |
| Uncertain | Any number | Unknown or any | No | Unknown or not done | |
| ^ Consistent with SCID: Two pathogenic variants in a known SCID gene; pathogenic variant in SCID gene on X chromosome in a male; ruled out 22q11 deletion; ruled out heterozygous TBX1 variants; ruled out homozygous or compound heterozygous FOXN1 mutations |
X-ALD
X-ALD (females)
| Category | Diagnosis | Plasma VLCFA | Plasmalogen | Mutation analysis | Fibroblast studies | Additional comments |
|---|---|---|---|---|---|---|
| Definite | Carrier Female | Normal | Normal | Pathogenic variant ABCD1 gene | Untested or unknown | |
| Definite | Carrier Female | Elevated^ | Normal | Pathogenic variant ABCD1 gene | Untested or unknown | |
| Possible | Carrier Female | Elevated^ | Not done/unknown | Not done/ unknown | ||
| Possible | Carrier Female | Not done/ unknown | Not done/unknown | Not done/ unknown | Not done/ unknown | Family history or family VLCFA studies suggestive of X-linked ALD |
| Definite | Carrier Female | Elevated^ | Normal | Variant of uncertain significance ABCD1 gene | ||
| Possible | Carrier Female | Normal | Normal | Variant of uncertain significance ABCD1 gene | ||
| ^In the pathogenic range |
X-ALD (males)
| Category | Plasma VLCFA | Clinical Symptoms | Plasmalogen | Mutation analysis | Family History |
|---|---|---|---|---|---|
| Definite | Elevated^ | Not present | Untested or unknown | Pathogenic Variant in ABCD1 gene | |
| Definite | Elevated^ | Not present | Normal | Deletion/ duplication identified in ABCD1 gene | |
| Definite | Elevated^ | Not present | Normal | No mutation on sequencing, deletion/ duplication not done | Family history or family VLCFA studies suggestive of X-linked ALD |
| Definite | Elevated^ | Not present | Normal | Variant of uncertain significance in ABCD1 gene | Family history or family VLCFA studies suggestive of X-linked ALD |
| Possible | Elevated^ | Not present | Normal | Variant of uncertain significance in ABCD1 gene | |
| Possible | Elevated^ | Not present | Normal | No mutation on sequencing, deletion/ duplication not done; Rule out other disorders of peroxisomal beta oxidation | |
| Possible | Elevated^ | Not present | Normal | Untested or unknown | |
| Probable | Not available | Not available | Not available | Pathogenic Variant in ABCD1 gene | |
| Possible | Not available | Not present | Not available | Variant of uncertain significance in ABCD1 gene | Family history or family VLCFA studies suggestive of X-linked ALD# |
| ^In the pathogenic range | |||||
| # Family history may include multiple relatives consistent with X-linked transmission as determined by clinical specialist: Maternal grandfather, maternal aunts, mother |
ABCD5 (in males and females)
| Category | Plasma VLCFA | Plasmalogen | Mutation analysis | Fibroblast studies | Clinical symptoms |
|---|---|---|---|---|---|
| Definite | Elevated^ | Normal | Two disease causing mutations | Untested or unknown | Not present at birth |
| Definite | Elevated^ | Normal | Untested or unknown | Consistent with ABCD5 | Not present at birth |
| ^In the pathogenic range |
Acyl-CoA Oxidase Deficiency (in males and females)
| Category | Plasma VLCFA | Plasmalogen | Mutation analysis | Fibroblast studies | Clinical symptoms |
|---|---|---|---|---|---|
| Definite | Elevated^ | Normal | Two pathogenic mutations in the ACOX1 gene | Untested or unknown | Not present at birth |
| Possible | Elevated^ | Normal | Untested or unknown | Consistent with Acyl-CoA Oxidase Deficiency | Not present at birth |
| ^In the pathogenic range |
CADDS
| Category | Plasma VLCFA | Clinical symptoms | Plasmalogen | Mutation analysis | Family history |
|---|---|---|---|---|---|
| Definite | Elevated^ | Present** | Normal | Deletion identified in ABCD1 and DXS1357E | |
| ^In the pathogenic range | |||||
| ** Symptoms may include: neonatal hypotonia, neonatal seizures, liver disease, neonatal cholestasis, sensorineural deafness |
D-bifunctional protein deficiency (in males and females)
| Category | Plasma VLCFA | Plasmalogen | Mutation analysis | Fibroblast studies | Clinical symptoms |
|---|---|---|---|---|---|
| Definite | Elevated^ | Normal | Two pathogenic mutations in the HSD17B4 gene | Untested or unknown | Present* |
| Possible | Elevated^ | Normal | Untested or unknown | Consistent with D-Bifunctional Protein | Present* |
| ^In the pathogenic range | |||||
| *Clinical symptoms may include: Hypotonia in newborn period, failure to thrive, craniofacial abnormalities, abnormal liver function tests. |
Non-peroxisomal disorder (in males and females)
| Category | Plasma VLCFA | Plasmalogen | Mutation analysis | Fibroblast studies | Clinical symptoms |
|---|---|---|---|---|---|
| Definite | Normal | Normal | Mutation in one of the 7 known genes for Aicardi-Goutières Syndrome | Untested or unknown | Present** |
| **Clinical symptoms may include: Hypotonia in newborn period, failure to thrive, on CT scan, intracranial calcifications. |
Peroxisomal disorder (in males and females)
| Category | Plasma VLCFA | Clinical symptoms | Plasmalogen | Mutation analysis | Family history |
|---|---|---|---|---|---|
| Probable | Elevated^ | Not present | Normal | No mutation on sequencing, deletion/duplication not found | |
| ^In the pathogenic range |
Zellweger spectrum disorder (in males and females)
| Category | Plasma VLCFA | Plasmalogen | Clinical symptoms | Mutation analysis | Fibroblast studies |
|---|---|---|---|---|---|
| Definite | Elevated^ | Low | Present* | Two pathogenic variants in the same PEX gene | Untested or unknown |
| Definite | Elevated^ | Low | Present* | Untested or unknown | Consistent with ZSD |
| Definite | Elevated^ | Low | Not present | Two pathogenic variants in the same PEX gene | Untested or unknown |
| Definite | Elevated^ | Low | Not present | Untested or unknown | Consistent with ZSD |
| Definite | Elevated^ | Low | Present* | Untested or unknown | Untested or unknown |
| Possible | Elevated^ | Low | Not present | Untested or unknown | Untested or unknown |
| Possible | Elevated^ | Normal | Not present | Untested or unknown | Untested or unknown |
| ^In the pathogenic range | |||||
| *Clinical symptoms may include: Hypotonia in newborn period, failure to thrive, craniofacial abnormalities, abnormal liver function tests. |
Enter Case Data