Long-chain 3-hydroxyacyl-CoA MS/MS Urine organic acid profile, urine acylglycine profile, plasma dehydrogenase deficiency (LCHAD)
Very long-chain acyl-CoA dehydrogenase MS/MS Urine organic acid profile, urine acylglycine profile, plasma deficiency (VLCAD)
Galactosemia GALT enzyme measurement GALT enzyme measurement, DNA mutations, galactose-1-P measurement
MS/MS Plasma amino acid profile, DNA mutations
In the United States the majority of infants diagnosed witha treatable metabolic disorder will be identified as a result of an abnormal newborn screen. Most states use tandem mass spectrometry to screen for a core panel of 29 disorders (Table 51-8). In most states, biotinidase deficiency and galactosemiaare typically screened for by evaluating enzyme function.
Strategy of Neonatal Screening
The purpose of neonatal screening is the early detection and rapid treatment of disorders before the onset of symptoms, thus preventing morbidity and mortality. In most states, infants are tested at 24 to 48 hours (see Chapter 58). A positive test demands prompt evaluation. Specific follow-up testing and treatment of an affected child depends on the disorder. Consistent with most screening tests, a significant proportion of infants who have a positive neonatal screening test do not have a metabolic disorder.
Neonatal screening is designed to maximize detection ofaffected infants but is not diagnostic. “Cutoff values” for eachtest are established carefully to identify infants with an elevated concentration of the substance or decreased activityof an enzyme with an acceptable number of false-positive results. A positive screening test must be followed by promptclinical assessment as recommended by the screening program and metabolic specialist. In many cases children willalso be provided therapy until the completion of definitive testing.
A positive screening test result causes anxiety for new parents; management of such anxiety is essential to minimize the harm of the program. In addition, definitive testing must be carried out promptly and accurately. If an inborn error of metabolism is excluded, parents need a thorough explanation of the results and reassurance that the infant is well. Such explanations will frequently require the expertise of a metabolic specialist or genetic counselor in the newborn period but may require reassessment by the primary care physician in the long term.
Specialized testing for inherited disorders of metabolism is effective in confirming a diagnosis suspected on the basis of an abnormal newborn screening result or on the basis of clinical suspicion. The tests that are helpful and examples of diagnoses made using these measurements depend on the deficient pathway in the disorder under consideration (Table 51-9).
Amino acid analysis is performed in plasma, urine, and cerebrospinal fluid. The plasma amino acid profile is most useful inidentifying disorders of amino acid catabolism. Amino acidsin the deficient pathway of the organic acid disorders may beabnormal, but often they are normal or may not be diagnostic.
Table 51-9 Specialized Metabolic Testing TEST ANALYTES MEASURED TEST HELPFUL IN IDENTIFYING DISORDERS Plasma amino acid profile Amino acids, including alloisoleucine PKU, urea cycle defects, tyrosinemias, MSUD, homocystinuria
Plasma total homocysteine Protein-bound and free homocysteine Homocystinuria, some forms of methylmalonic acidemia
Urine amino acid profile Amino acids Disorders of amino acid renal transport
Plasma acylcarnitine profile Acylcarnitine derivatives of organic and Organic acid disorders, fatty acid oxidation disorders fatty acid catabolism
Urine acylglycine profile Acylglycine derivatives of organic and Organic acid disorders, fatty acid oxidation disorders fatty acid catabolism