Clinical Information

Xanthine and hypoxanthine are the direct precursors of uric acid, the end product of purine metabolism. Two inborn errors of metabolism are characterized by elevated excretion of xanthine and hypoxanthine. Patients with isolated xanthine dehydrogenase (XDH, xanthine oxidase) deficiency may remain asymptomatic, but nephrolithiasis, due to the insolubility of xanthine, may occur at any age. Some patients also develop a myopathy with crystalline xanthine deposits in muscle. Combined deficiency of XDH and the related enzyme sulfite oxidase (SO) is also characterized by nephrolithiasis, but more prominently by the symptoms of SO deficiency (isolated SO deficiency also occurs) including neonatal seizures, myoclonus, lens dislocation, and severe mental retardation. This form of xanthinuria is caused by molybdenum cofactor deficiency, which is required for the activity of both oxidases. Elevations of xanthine and hypoxanthine and abnormally low levels of uric acid are found in both disorders, while in patients with XDH/SO deficiency sulfites and sulfur-containing metabolites (S-sulfocysteine, thiosulfate, taurine) also accumulate.

Analysis of xanthine and hypoxanthine alone, allows the diagnosis of xanthinuria, is helpful for the evaluation of low serum and/or urine uric acid concentrations, and for the evaluation of allopurinol (a xanthine oxidase inhibitor) treatment in hyperuricemic disorders (eg, Lesch-Nyhan syndrome).