Detection of Heterozygotes for Phenylketonuriaby Constant Intravenous Infusionof L-Phenylalanine

W measured therate of elimination of phenylalanine by constant intravenous infusion of L-phenylalanine in 14 parents of children with phenylketonuria and in21 subjects with a negative family history for this disease. When re-ciprocals of the observed elimination rates were plotted against the reciprocals of the increase in the plasma phenylalanine concentrations, approximately straight lines resulted.The theoreticalmaximum eliminationrate,the mean value for which was 32 mmol/h inthereference subjects,was reduced by 41 % inthe 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 phenylke-tonuric heterozygotes than in the reference subjects at the same rate of elimination of phenylalanine indicated an increasedrateofeliminationoftyrosineata fixedcon-centration of this amino acid in these subjects. AddItional Keyphrases: tyrosine clearance- inherited disorders- diagnostic aids- phenylalanine/tyrosine rela-tionships ‘ sex- and age-related differences ‘ elimination kinetics For assessment of the metabolism of single amino acids,differentkindsofloadingtestscan be used.We studied the kinetics of phenylalanmne after a single in-travenous loading and found that its elimination from plasma could be adequately described by assuming a two-compartment model and first-order kinetics. This implies that the elimination rate constant from the centralcompartment isassumed tobe thesame within a ratherwide rangeofconcentration.By thismethod we studied the kinetics of L-phenylalanine in patients with cirrhosis of the liver (1) and in heterozygotes for phen-ylketonuria (2)