Phenylketonuria

PKU is the prototype disorder for newborn screening. Widespread newborn screening for this condition has been in place since the mid- to late 1960s. Newborns with this condition are typically asymptomatic, and by the time that clinical findings are observed, irreversible central nervous system damage has occurred. Treatment initiated in the first 2 weeks of life can result in a normal outcome. In essentially all cases, it results in marked amelioration of the clinical phenotype. All newborns should be screened for PKU.

Newborn screening is performed by measuring phenylalanine (phe) in blood spotted on filter paper ≥24 hours after feeding at birth. If the phe level is above a cutoff established by the laboratory, the infant is identified as a candidate for further testing. If the phe level is repeated in plasma and found to be elevated, with no evidence on further testing for a defect in tetrahydrobiopterin (BH4) synthesis or recycling, the diagnosis of phenylalanine hydroxylase (PAH) deficiency is established. Inborn errors of BH4 synthesis can also cause hyperphenylalaninemia. It is essential to exclude at this stage because treatment for defects in BH4 synthesis is different from treatment for PKU. Once the diagnosis of PAH deficiency is confirmed, further subclassification as PKU or hyperphenylalaninemia will depend on the extent of the plasma phe elevation, both initially and as the infant's diet becomes more varied during the course of the first year of life.