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April 20, 1984

Prenatal Diagnosis of Classical Phenylketonuria by Gene Mapping

Author Affiliations

From the Department of Cell Biology, Baylor College of Medicine, and Howard Hughes Medical Institute, Houston (Drs Woo, Thirumalachary, and Robson and Mr Lidsky); and the John F. Kennedy Instituttet, Glostrup, Denmark (Dr Güttler).

JAMA. 1984;251(15):1998-2002. doi:10.1001/jama.1984.03340390052029

CLASSICAL phenylketonuria (PKU) is caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase and is a typical example of an inborn error of metabolism.1-3 The normal metabolic pathway of the aromatic amino acid is shown in Fig 1. Deficiency of phenylalanine hydroxylase causes the accumulation of phenylalanine and phenylalanine metabolites to excessively high levels and a depletion of serum tyrosine.4 Without early detection followed by rigid dietary correction during the first decade of life,5 children with classical PKU will develop severe mental retardation. The disease is transmitted as an autosomal recessive trait and has a prevalence of about one in 10,000 births among whites.6 It has also been estimated that one in 50 whites in the population is a carrier of the gene for the disease.7

In many Western countries, neonatal screening for PKU by the Guthrie test8 is mandated by law, and dietary intervention