After completing this article, readers should be able to: 1. List the initial laboratory tests used to assess the infant suspected of having an inborn error of metabolism. 2. Delineate the most common cause of a decreased anion gap. 3. List the specialized tests that should be undertaken in neonates suspected of having inborn errors of metabolism. Approximately 4% of individuals born in the United States have a genetic or partly genetic disorder. Inborn errors of metabolism contribute significantly to this total. Although individually rare, the aggregate incidence of metabolic disease is relatively high and may be greater than 1 in 1,000 newborns. Newborn screening programs using tandem mass spectrometry that can detect approximately 20 inborn errors of metabolism typically have reported an incidence of 1 in 5,000. Because there are hundreds of known metabolic conditions, the aggregate estimate seems reasonable. Relatively few metabolic diseases produce symptoms in the neonate. Many disorders, such as the sphingolipidoses, mucopolysaccharidoses, purine and pyrimidine disorders, and neuronal ceroid lipofuscinoses, produce slowly progressive encephalopathies, although histologic abnormalities may be present in the fetal central nervous system by 4 to 5 months of gestation. Because inborn errors of metabolism that present in the newborn period often have nonspecific features, appropriate laboratory investigations are required to avoid misdiagnoses such as sepsis or asphyxia. Many medical centers are not equipped to perform the specialized investigations needed to evaluate a patient in whom an inborn error of metabolism is suspected, such as detailed amino acid, organic acid, or acylcarnitine analyses. However, simple laboratory tests, including measurements of blood gases, electrolytes, glucose, lactate, and ammonia levels and basic urinalysis, often provide the initial clues to a possible underlying metabolic disease. Although the presence of a specific inborn error of metabolism cannot be confirmed until biochemical genetic laboratory results are available, a diagnosis may …