Four patients in a kindred who have had hyperuricemia, uric acid crystalluria and stones, were found to have partial deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity. The pattern of inheritance is consistent with the observation that the activity of HGPRT is determined by a gene on the X chromosome. The patients have normal intelligence, do not display self-mutilation and do not have gouty arthritis. In two patients, both children, confirmatory evidence of overproduction of uric acid was obtained following the administration of isotopically labeled uric acid and glycine. In both of these patients cerebrospinal fluid levels of hypoxanthine were two to three times those of normal controls. In all patients the administration of allopurinol reduced the amount of uric acid in blood and urine, but a concomitant increase in the levels of hypoxanthine and xanthine occurred in two patients. This observation is consistent with the hypothesis that the HGPRT enzyme is necessary for the reutilization of hypoxanthine. In both of the affected children persistent acidity of the urine and a reduction in urinary ammonium excretion were noted before therapy was initiated. Renal function, histology of the renal cortex and renal glutaminase enzyme activities were normal in these two patients. In both patients urinary ammonium excretion increased following allopurinol therapy. This suggests that a high urate load presented to the kidney may alter ammonia production or excretion.
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