A simple test for heterozygosity for phenylketonuria

Abstract

Thirty-six known heterozygotes for phenylketonuria, and 47 control subjects were tested for heterozygosity by determination of fasting serum phenylalanine and tyrosine concentrations. In addition, intravenous phenylalanine loading tests were performed on 23 subjects from each group. Intravenous administration of the phenylalanine load failed to improve the discriminating ability of oral phenylalanine loading tests reported by other investigators. Combined use of the fasting serum or plasma phenylalanine concentration and the fasting phenylalanine-tyrosine ratio allows accurate classification of approximately two-thirds of all subjects as to heterozygosity, and leaves approximately onethird unclassified. This test is much simpler than any loading test. It is suggested that it be employed as an aid to genetic counselling of close relatives of phenylketonurics, and as an additional diagnostic check for asymptomatic infants who are thought to have phenylketonuria and are under treatment with a low-phenylalanine diet.