- Argininosuccinic Acidemia (ASA)
- Biotinidase Deficiency
- Congenital Adrenal Hyperplasia
- Congenital Hypothyroidism
- Citrullinemia (Types I & II)
- Cystic Fibrosis
- Fatty Acid Oxidation Disorders (11)
- Medium Chain Acyl-CoA Dehydrogenase Deficiency
- Long Chain 3-Hydroxyacyl CoA Dehydrogenase Deficiency
- Trifunctional Protein Deficiency
- Very Long Chain Acyl-CoA Dehydrogenase Deficiency
- Carnitine Palmitoyltransferase Deficiency Type II
- Carnitine/Acylcarnitine Translocase Deficiency
- Glutaric Acidemia Type II
- 2,4 Dienoyl-CoA Reductase Deficiency
- Carnitine Uptake Defect
- Medium/Short Chain Hydroxylacyl CoA Dehydrogenase
- Medium Chain 3-Ketoacyl CoA Thiolase Deficiency
- Hyperphenylalaninemia (see PKU)
- Maple Syrup Urine Disease
- Organic Acidemias (12)
- Glutaryl CoA Dehydrogenase Deficiency Type I
- Propionyl CoA Carboxylase Deficiency
- Methylmalonic Acidemia:
- Isovaleryl CoA Dehydrogenase Deficiency
- 3-Methylcrontonyl CoA Carboxylase Deficiency
- Multiple CoA Carboxylase Deficiency
- 3 Methylglutaconyl CoA Hydratase Deficiency
- Mitochondrial Acetoacetyl CoA Thiolase Deficiency
- 2-Methyl-3-Hydroxybutyryl CoA Dehydrogenase
- 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
- Phenylketonuria (PKU)
- Severe Combined Immune Deficiency (SCID)
- Tyrosinemia (Types I, II & III)
NOTE: Newborn screening cannot differentiate ASA from citrullinemia.
Autosomal recessive urea cycle disorder caused primarily by a deficiency in argininosuccinic acid (ASA) lyase enzyme activity causing the build-up of argininosuccinic acid, citrulline, and ammonia in the blood. Clinical symptoms include lack of appetite, vomiting, listlessness, seizures, and coma.
Autosomal recessive disorder of biotin recycling that leads to multiple carboxylase deficiencies. Individuals with biotinidase deficiency cannot recycle endogenous biotin and cannot release dietary protein-bound biotin.
NOTE: Newborn screening cannot differentiate citrullinemia from ASA.
Autosomal recessive urea cycle disorder caused primarily by a deficiency in the argininosuccinic acid synthetase enzyme activity causing the build-up of the amino acid citrulline and ammonia in the blood. Clinical symptoms include lack of appetite, vomiting, listlessness, seizures, and coma.
A family of diseases whose common feature is an enzymatic defect in the steroidogenic pathway leading to the biosynthesis of cortisol. The 21-hydroxylase deficiency accounts for 90-95% of CAH cases, resulting in ambiguous genitalia in females and salt-losing crisis in either males or females. Early detection and treatment is essential to prevent death in infants with salt-losing CAH. See Guidelines for Proper Follow-up of 17-OHP Results.
COMMENT: Repeat of non-normal 17-OHP newborn screening tests by a “reference” laboratory is not recommended due to the potential confusion in reporting units.
Disorders of the thyroid-hypothalamus-pituitary axis resulting in inadequate production of thyroid hormones. Hypothyroidism is a family of disorders, including endemic cretinism, thyroid agenesis or ectopia, genetic disorders of thyroid hormonogenesis, or hypopituitarism.
COMMENT: TSH increases dramatically shortly after birth and gradually returns to adult normal levels in about 72 hours. False positive results occur due to the specimen being collected at the height of the TSH spike, usually within the first hours of life. Although newborn screening can detect “primary” hypothyroidism with a high degree of accuracy, other forms of hypothyroidism may develop in the weeks after birth. The physician must therefore remain alert to clinical symptoms in older infants despite normal newborn screening results. Perform serum total T4, free T4, and TSH if any doubt exists.
Autosomal recessive disorder characterized by pulmonary obstruction and/or exocrine pancreatic dysfunction. The most common mutation causing cystic fibrosis is a three-basepair deletion (F508del) in the cystic fibrosis transmembrane regulator (CFTR) gene.
COMMENT: Screening for cystic fibrosis using the two-tiered IRT/DNA approach cannot always distinguish babies who are CF carriers from babies who are affected. Sweat Chloride testing by the CFF-approved quantitative pilocarpine ionotophoresis method is recommended for all reported positive screening results, i.e., babies with either one or two mutations detected. For babies with no detectable mutations but with an IRT >170ng/mL, the primary care provider should be alert for persistent diarrhea, poor weight gain, chronic cough or respiratory problems. If these signs appear, or if there is a family history of CF, contact should be made with a CF specialist.
FDA-cleared 139 Variant Panel
Expanded CF Mutations – PILOT STUDY
WSLH is currently conducting a pilot study (funded by the Legacy of Angels Foundation) that assesses the utility of a more inclusive mutation panel. The mutations are listed in the following table.
Non-FDA Approved Variant Panel
Fatty Acid Oxidation Disorders (FOD) are a class of inborn errors of metabolism in which there is an enzyme defect in the fatty acid metabolic pathway (use of dietary and stored fat). Clinical symptoms of FOD disorders include hypotonia, lethargy and vomiting; the hypoglycemia can lead to coma, encephalopathy, hepatic failure or death.
Autosomal recessive disorder of galactose metabolism. The genetic disturbance is expressed as a cellular deficiency of either galactose-1-phosphate uridyl transferase (classic form), galactokinase (variant), or uridine diphosphate galactose 4 epimerase (variant) – the enzymes catalyzing the reaction by which galactose is converted to glucose. The main dietary source of galactose is lactose, the principle carbohydrate in milk.
COMMENT: Transfusion with red blood cells may cause GALT enzyme activity to appear falsely normal. Total galactose will be performed on specimens from newborns that have been transfused. If the newborn is receiving lactose-free formula at the time of collection, there is risk of a falsely normal galactose result. Galactosemia screening for newborns, both transfused and receiving a lactose-free diet, are considered inconclusive. Repeat the newborn screen when the lactose-free formula has been discontinued.
Screening for galactosemia using the GALT enzyme test will NOT detect galactosekinase or uridine diphosphate galactose 4 epimerase.
A group of autosomal recessive disorders characterized by synthesis of abnormal hemoglobin molecules (e.g., S, E, C, D) or decreased synthesis of a beta globin chain. Those hemoglobinopathies characterized by synthesis of an abnormal molecule are detectable at birth. Affected individuals with sickle cell disease may have early overwhelming sepsis and require prompt evaluation at a comprehensive care facility.
*If a baby has been transfused or a transfusion is imminent, see When to Collect a Specimen
COMMENT: Persons with hemoglobin traits are by definition carriers of an abnormal hemoglobin gene. While this fact has little clinical significance to the individual, genetic counseling is important (especially sickle cell trait (FAS)) because both parents may also be carriers creating a significant risk for a future baby to have a hemoglobin disease (i.e., sickle cell disease).
Any concern for the rare symptomatic variant (non-sickle) can be monitored through clinical observations (anemia, jaundice, cyanosis) combined with a hemoglobin electrophoresis, CBC, and reticulocyte count. By one year of age, some children may show a mild microcytic anemia. The presence of Barts hemoglobin is an exception as it may be clinically significant, especially in Southeast Asians. Specific hematologic consultation is recommended for babies who show Barts hemoglobin at newborn screening. Recommended follow-up at one year of age is CBC, reticulocyte count, and hemoglobin quantitation.
Hyperphenylalaninemia (see PKU)
Autosomal recessive amino acid disorder caused primarily by a deficiency in cystathionine beta synthase enzyme activity causing the build-up of the amino acid methionine in the blood. Early detection and treatment can prevent associated mental retardation, seizures, motor development delays, weakening of bones, and venous and arterial blood clots.
(Hyperphenylalaninemia and Biopterin [BN4] Cofactor defects of regeneration and biosynthesis)
Autosomal recessive hyperphenylalanemia caused primarily by a deficiency of phenylalanine hydroxylase activity, or impaired synthesis, or recycling of the biopterin (BN4) cofactor. Early detection and treatment is essential to prevent associated mental retardation.
COMMENT: The use of quantitative phenylalanine measurements increases the ability to detect PKU earlier in the baby’s life than previously used qualitative assays. This, and the fact that phenylalanine levels are often (greater than 90% of the time) above normal at birth and continue to rise in the first hours of life, decrease the need for a protein feeding for the detection of PKU. The program has detected PKU in babies when specimens were collected before 8 hours of age and prior to a protein feeding.
Autosomal recessive amino acid disorder caused by deficiencies in the branched chain keto-acid dehydrogenase enzymes causing the build-up of leucine, isoleucine, and valine in the blood. Early detection and treatment is essential to prevent associated mental retardation and/or neurological complications.
Organic Acidemias (OA) are a class of inherited metabolic disorders that lead to accumulation of organic acids in biological fluids (blood and urine). This, in turn, produces disturbances in the acid-base balance and causes alterations in pathways of intermediary metabolism. Clinical symptoms of OA disorders may include vomiting, metabolic acidosis, ketosis, dehydration or coma, hyperammonemia, lactic acidosis, hypoglycemia, failure to thrive, hypotonia, global developmental delay, sepsis and hematological disorders.
Severe Combined Immune Deficiency (SCID) is a group of inherited diseases that result in a lack of T-cells and severely reduced B-cell function. The mode of inheritance may be X-linked or autosomal recessive. Babies with SCID are extremely susceptible to infection and die early in life unless treated with allogeneic bone marrow transplantation.
COMMENT: Since the diagnosis of SCID can be difficult, it is recommended that one of the state’s pediatric immunology specialists be consulted for proper follow-up when abnormal results are reported from the screening laboratory. A list of specialists is provided on the written report issued by the newborn screening laboratory.
Autosomal recessive amino acid disorder caused by a deficiency in fumarylacetoacetate hydrolase enzyme activity causing the build-up of the amino acid tyrosine in the blood. Early detection and treatment is successful in preventing poor growth, liver damage, swelling of the legs, and inappropriate bleeding.
Newborn Point-of-Care Screening