Detection of heterozygotes for phenylketonuria by constant intravenous infusion of L-phenylalanine.

We measured the rate of elimination of phenylalanine by constant intravenous infusion of L-phenylalanine in 14 parents of children with phenylketonuria and in 21 subjects with a negative family history for this disease. When reciprocals of the observed elimination rates were plotted against the reciprocals of the increase in the plasma phenylalanine concentrations, approximately straight lines resulted. The theoretical maximum elimination rate, the mean value for which was 32 mmol/h in the reference subjects, was reduced by 41% in the phenylketonuric heterozygotes. The elimination rate at an increase in plasma phenylalanine concentration of 0.5 mmol/liter discriminated the phenylketonuric heterozygotes from normal homozygotes, with no overlap between the groups. A lower plasma tyrosine concentration in the phenylketonuric heterozygotes than in the reference subjects at the same rate of elimination of phenylalanine indicated an increased rate of elimination of tyrosine at a fixed concentration of this amino acid in these subjects.