Newborn Screen

See Also

Inborn Errors of Metabolism

Epidemiology

Newborn Screening identifies significant conditions in 5000 to 6000 newborns per year in U.S.

Protocol
Testing

Testing scope varies by state
1. Universal Newborn Screening varies by U.S. state
  1. http://genes-r-us.uthscsa.edu/resources/consumer/statemap.htm
2. Recommended Uniform Screening Panel (Standardized recommendations for U.S. State screening)
  1. https://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/recommendedpanel/
Timing
1. Before newborn hospital discharge (typically at 24-48 hours of life)
2. Results are typically available within 24 hours
3. Consider repeat testing at 1-6 weeks of life (routinely done in 14 states)
Costs
1. Most states have fee based testing (mean cost $76)
2. Opt-Out policies are available for parents

Labs
Standard Core Condition newborn metabolic screening

Amino Acid disorder screening
1. Homocystinuria (HCY)
2. Maple syrup urine disease (MSUD)
3. Classic Phenylketonuria (PKU)
4. Tyrosinemia Type I (Tyr-1)
Fatty Acid oxidation disorder screening
1. Carnitine Uptake Defect or carnitine transport defect (CUD)
2. Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
3. Long-chain acyl-CoA dehydrogenase deficiency (LCHAD)
4. Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD)
5. Trifunctional Protein deficiency (TFP)
Organic acid disorder screening
1. 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC)
2. Beta-ketothiolase deficiency (ßKT)
3. Glutaric acidemia type I (GA1)
4. 3-hydroxy-3-methylglutaryl-CoA lyase deficiency or 3-Hydroxy-3-methyglutaric aciduria (HMG)
5. Isovaleric acidemia (IVA)
6. Holocarboxylase synthase deficiency or Multiple carboxylase deficiency (MCD)
7. Propionic acidemia (PROP)
8. Methylmalonic acidemia
  1. Methylmalonyl-CoA mutase (MUT)
  2. Cobalamin A and B defects (Cbl A, Cbl B)
Urea Cycle Disorder Screening
1. Argininosuccinic Acidemia or Aciduria (ASA)
2. Citrullinemia Type 1 (CIT)
Endocrine Disorder Screening
1. Congenital Adrenal Hyperplasia (CAH)
Hemoglobinopathy Screening
1. Sickle Cell Anemia (Hb SS)
2. S, ßeta-Thalassemia (Hb S/ßTh )
3. S,C disease (Hb S/C)
Other Screening
1. See Newborn Hearing Screening
2. Biotinidase deficiency (BIOT)
3. Critical Congenital Heart Disease (CCHD)
4. Cystic Fibrosis (CF)
  1. Based on Immunoreactive Trypsinogen (IRT) DNA
5. Classic Galactosemia (GALT)
6. Glycogen Storage Disease Type II or Pompe Disease (GSD II)
7. Severe combined Immunodeficiencies (SCID)
8. Mucopolysaccharidosis Type I (MPS I)
9. X-linked Adrenoleukodystrophy (X-ALD)

Lab
Secondary Condition newborn metabolic screening

An addition 26 or more conditions may be detected on Newborn Screening

Interpretation

False Positive tests are common (up to 60 False Positives for every true positive)
1. Cut-off values are set low to prevent missing actual cases
Borderline results should be immediately retested
Positive results require immediate evaluation
1. American College of Medical Genetics ACT sheets guide management (see below)

Resources

American College of Medical Genetics ACT sheets
1. http://www.acmg.net/Admin/ACT_Sheets_and_Confirmatory_Algorithms/NBS_ACT_Sheets_and_Algorithm_Table/ACMG/Resources/ACT_Sheets_and_Confirmatory_Algorithms/NBS_ACT_Sheets_and_Algorithms_Table.aspx?hkey=aa84b9b4
Professional Resources (National Newborn Screening and Global Resource Center)
1. http://genes-r-us.uthscsa.edu/resources.htm
HRSA Advisory Committee on Heritable Disorders in Newborns and Children
1. https://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/recommendedpanel/
Newborn Screening Fact Sheets (AAP)
1. http://pediatrics.aappublications.org/content/118/3/e934?sid=8e387814-ea2b-4a20-817f-a923ca0eddde
Acute Illness protocols (New England Consortium of Metabolic Programs)
1. http://newenglandconsortium.org/for-professionals/acute-illness-protocols/

References