Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

Abstract

We tested the hypothesis that there is an enhanced rate of hy- poxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with 18-'4Cladenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme- deficient patients and 6.00.7% (meanSE) in four normal sub- jects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 106 cpm/g creatinine in both patients and to 4.730.69 X 106 cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 39886% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 gM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xan- thinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predom- inance of this urinary purine compound in xanthinuria.