Prenatal diagnosis and carrier detection of classic phenylketonuria by gene analysis.
1984; National Institutes of Health; Volume: 74; Issue: 3 Linguagem: Inglês
Autores Tópico(s)
Diet and metabolism studies
ResumoPhenylketonuria (PKU) is a human genetic disorder caused by an inborn error in aromatic amino acid metabolism. It was first observed approximately 50 years ago that patients with this condition had excess phenylpyruvate in the urine.1 Subsequently, it was discovered that in such patients the liver was unable to convert phenylalanine to tyrosine which is the major pathway of phenylalanine catabolism2-5 (Fig 1). Classic PKU is thus characterized by a lack of phenylalanine hydroxylase activity in the liver.6 The lack of this enzymatic activity causes persistent hyperphenylalaninemia, and the clinical symptom is an irreversible impairment of brain development resulting in severe mental retardation in untreated children.1,7 Phenylalanine hydroxylase deficiency, regardless of phenotypic variations, is transmitted as an autosomal recessive trait. A simple method for mass screening involving the determination of phenylalamine in small samples of blood from newborn infants was developed by Guthrie and Susi.8 Neonates whose PKU was detected by this test can be treated with a (corrective) diet low in phenylalanine content.9-11 At the present time, there is no diagnostic method available for the detection of affected homozygotes in utero. The development of methodologies for prenatal diagnosis and definitive carrier detection of this genetic disorder are subjects of the present discussion. It should be emphasized that our work involves only the gene for phenylalanine hydroxylase and deals strictly with classic PKU. It has nothing to do with various forms of atypical phenylketonuria that can be due to the deficiency of dihydropteridine reductase or biopterin synthetase or other enzyme systems.11
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