Present newborn screening for phenylketonuria

Newborn screening for phenylketonuria (PKU) began in the United States in t he early 1960s following development of the Guthrie bacterial inhibition as say that allowed for the easy, rapid screening of elevated blood phenylalan ine levels collected on newborn filter paper samples. Since that time, a nu mber of other techniques that screen for PKU, other inborn errors of metabo lism, and a variety of nonmetabolic disorders have been developed using new born blood samples. The most advanced, comprehensive technique available to day is tandem mass spectrometry (MS-MS), which simultaneously identifies an d measures many compounds of varying structural classes allowing for concur rent screening of many disorders, including aminoacidemias, organic aciduri as, and fatty acid disorders. Despite this progress in presymptomatic neonatal detection of PKU, there ar e some difficulties with newborn screening. These include false-positive re sults, occasional missed diagnoses, and problems surrounding early discharg e. In addition, not all elevated phenylalanine levels are a result of a def iciency of the liver enzyme phenylalanine hydroxylase (PAH). Some infants h ave transiently elevated levels. Others have defects in the synthesis or re cycling of tetrahydrobiopterin (BH4), the cofactor of PAH, and some have se condary phenylalanine elevations due to disorders that affect the liver, su ch 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, dieta ry or cofactor therapy. (C) 1999 Wiley-Liss, Inc.