Cystinylglycine in plasma: diagnostic relevance for pyroglutamic acidemia, homocystinuria, and phenylketonuria.

Cystinylglycine, recently identified as a normal small peptide in human plasma, has diagnostic importance for several genetically determined disorders. We found cystinylglycine absent from the plasma of a patient with pyroglutamic acidemia, and the peptide was either absent or greatly reduced in plasma from patients with homosyctinuria. In the latter disorder, a different small peptide replaced cystinylglycine. It was identified as the mixed disulfide of homocysteine and cysteinylglycine. The mean plasma concentration of cystinylglycine was 13.6 +/- 3.6 mumol/l in adult control subjects, and concentrations of the mixed disulfide of homocysteine and cysteinylglycine varied between 2 and 10 mumol/l in the plasma of homocystinuric patients. Failure to separate cystinylglycine from phenylalanine with many rapid amino acid analyzer systems can lead to a misclassification of persons as heterozygotes for the phenylketonuria gene when heterozygosity testing is based on the phenylalanine/tyrosine molar ratio in fasting plasma.