Overproduction of uric acid in hypoxanthine-guanine phosphoribosyltransferase deficiency. Contribution by impaired purine

salvage to the hyperuricemia associated with hypo-xanthine-guanine phosphoribosyltransferase deficiency was measured by the intravenous administration of tracer doses of [8-14C]adenine to nine patients with normal enzyme activity, three patients with a partial deficiency of hypoxanthine-guanine phosphoribosyl-transferase, and six patients with the Lesch-Nyhan syndrome. The mean cumulative excretion of radio-activity 7 d after the adenine administration is 5.6+2.4, 12.9±0.9, and 22.3±4.7 % of infused radioactivity for control subjects, partial hypoxanthine-guanine phos-phoribosyltransferase-deficient subjects, and Lesch-Nyhan patients, respectively. To assess relative rates of nucleotide degradation in control and hypoxanthine-guanine phosphoribosyltransferase-deficient patients two separate studies were employed. With [8-'4C]inosine administration, three control subjects excreted 3.7-8.5% and two enzyme-deficient patients excreted 26.5-48.0% of the injected radioactivity in 18 h. The capacity of the nucleotide catabolic pathway to accelerate in response to D-fructose was evaluated in control and enzyme-deficient patients. The normal metabolic response to intravenous fructose is a 7.5+4.2-mmol/g creatinine increase in total urinary purines during the 3-h after the infusion. The partial hypoxanthine-guanine phospho-ribosyltransferase-deficient subjects and Lesch-Nyhan patients show increases of 18.6±10.8 and 17.3+11.8 mmol/g creatinine, respectively. Of the observed rise in purine exretion in control subjects, 40 % occurs from Dr. Edwards is a Rheumatology Fellow from the Rackha