Xanthine oxidase deficiency: studies of a previously unreported case.

Xanthinuria is a familial disorder of purine metabolism that results from a marked deficiency of xanthine oxidase (EC 1.2.3.2) activity. We report here the clinical and biochemical features of a new case of xanthinuria. Serum urate concentration was 0.8 mg/i 00 ml, urinary uric acid excretion was 16 mg per day, urinary oxypurme excretion was 1630 mol per day, and total purine excretion was 314 mg per day. After allopurinol was administered, total purine excretion was 323 mg per day and erythrocyte phosphoribosylpyrophosphate content was unchanged. The ratio (by wt) of xanthine to hypoxanthine in the urine was 4.6 before and 9.6 after allopurinol was administered to this patient. Both allopurinol and oxipurinol were detectable in urine. Orotic acid and orotidine excretion increased from undetectable amounts (<2 mg per day) to 47 and 86 mg per day, respectively. These data suggest that this xanthinuric subject has a markedly decreased xanthine oxidase activity, although some residual activity may be functional in vivo. It is probable that he re-utilizes purine so extensively that hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) isvirtually saturated with hypoxanthine and xanthine in vivo. In addition, these data indicate that the increase in orotic acid and orotidine seen in normal and gouty subjects taking allopurinol is not a direct consequence of xanthine oxidase inhibition, but probably an effect of allopurinol or one of its metabolites on pyrimidine biosynthesis.