Newborn screening for phenylketonuria (PKU) began in the United States in the early 1960s following development of the Guthrie bacterial inhibition assay that allowed for the easy, rapid screening of elevated blood phenylalanine levels collected on newborn filter paper samples. Since that time, a number of other techniques that screen for PKU, other inborn errors of metabolism, and a variety of nonmetabolic disorders have been developed using newborn blood samples. The most advanced, comprehensive technique available today is tandem mass spectrometry (MS-MS), which simultaneously identifies and measures many compounds of varying structural classes allowing for concurrent screening of many disorders, including aminoacidemias, organic acidurias, and fatty acid disorders.
Despite this progress in presymptomatic neonatal detection of PKU, there are some difficulties with newborn screening. These include false-positive results, occasional missed diagnoses, and problems surrounding early discharge. In addition, not all elevated phenylalanine levels are a result of a deficiency of the liver enzyme phenylalanine hydroxylase (PAH). Some infants have transiently elevated levels. Others have defects in the synthesis or recycling of tetrahydrobiopterin (BH 4 ), the cofactor of PAH, and some have secondary phenylalanine elevations due to disorders that affect the liver, such as tyrosinemia or galactosemia. Several of these problems, including the number of false positives, may be eliminated by pattern identification via MS-MS.
Once identified with a significant or persistent elevation in phenylalanine, infants and their families are referred to a metabolic center for further evaluation, including repeat quantitative testing and, if necessary, dietary or cofactor therapy.
1999 Wiley-Liss, Inc.