An enzymatic basis for variation in response to allopurinol. Hypoxanthine-guanine phosphoribosyltransferase deficiency.

Abstract

Although allopurinol appears to decrease the rate of de novo purine biosynthesis, this effect is variable in gout, possibly because uric acid production is increased in patients who are relatively deficient in hypoxanthine-guanine phosphoribosyltransferase (HG-PRTase). To test this possibility, allopurinol was given to 11 patients with excessive uric acid production. In seven allopurinol had no effect on total excretion of purine catabolites. The same seven had a marked decrease in the activity of HG-PRTase and were also resistant to the effects of allopurinol on purine synthesis. These observations suggest that HG-PRTase activity is necessary for allopurinol to suppress purine synthesis de novo in man. This effect of allopurinol was also absent in four additional gouty patients with normal uric acid production and normal HG-PRTase activity. Hence, deficiency of this enzyme does not account for all cases of resistance to suppression of de novo purine biosynthesis by allopurinol.