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This study examined whether increased purine biosynthesis de novo in HGPRT deficiency contributes to adenine nucleotide formation compared with normal subjects. Four HGPRT deficient patients and four normal subjects received intravenously 10 to 25 microCi of [8-14C]adenine to radiolabel the adenine nucleotide pool followed five days later by a rapid infusion of fructose to stimulate purine nucleotide degradation. Fructose infusion increased urinary radioactivity in the enzyme-deficient patients to 141% +/- 13% (mean +/- SEM) of the baseline values compared with 1,067% +/- 102% in normal subjects (P less than .01). The absolute mean increase in total urinary purines in the patients was 17.96 +/- 3.36 and 10.38 +/- 3.80 mmol/g creatinine in controls (P less than .05). The apparent specific radioactivity of urinary purines increased in the control group from a mean of 1.29 X 10(5) to 3.64 X 10(5) cpm/mmol of purines (P less than .02) but decreased in the enzyme-deficient subjects from a mean of 1.66 X 10(5) to 1.38 X 10(5) cpm/mmol. To assess if the decrease in the specific activity of urinary purines was due to an elevated rate of de novo purine synthesis, two HGPRT-deficient patients were treated with allopurinol and adenine followed five days later by a fructose infusion. The administration of adenine increased the specific activity of urinary purines after the infusion of fructose from a mean baseline value of 1.05 X 10(5) to 1.42 X 10(5) cpm/mmol of purines.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: The renal excretion of uric acid is usually diminished in primary gout with respect to increased serum urate levels. To determine whether the renal excretion of uric acid precursors, hypoxanthine and xanthine, is also abnormal in primary gout, the concentrations of these purines were measured in plasma and 24-hour urine samples in normal subjects, in patients with primary gout and uric acid underexcretion, and in patients with enzyme deficiencies that are known to result in over-production of uric acid., Subjects and Methods: Three groups of subjects were studied: Group I consisted of 10 ambulatory healthy normal men; Group II consisted of 15 patients in whom primary gout was diagnosed; and Group III consisted of 10 patients with various enzyme defects known to produce an excessive synthesis of uric acid. In each subject, plasma and 24-hour urinary uric acid, hypoxanthine, xanthine, and creatinine concentrations were measured and the mean of three consecutive determinations was used. The fractional excretion of purine compounds was calculated from a formula. Hypoxanthine phosphoribosyltransferase, adenine phosphoribosyltransferase, and hemoglobin were also measured in each subject., Results: Plasma hypoxanthine and xanthine were increased in the two groups of patients compared with the control subjects. Urinary hypoxanthine and xanthine levels were reduced in gouty patients compared with control subjects, whereas levels were increased in patients with uric acid overproduction. A positive correlation was found between the renal clearances of uric acid, hypoxanthine, and xanthine., Conclusion: The results indicate that the renal excretion of hypoxanthine and xanthine is severely impaired in most patients with primary gout.

Monitoring of plasma oxypurinol has been proposed to prevent allopurinol side effects. An 89-year-old man developed a severe desquamative rash, fever, eosinophilia, hepatocellular injury and renal failure after allopurinol administration. Eight hours after the last dose, plasma allopurinol was undetectable and plasma oxypurinol was 50 mumol/l. This is the first case in which severe allopurinol hypersensitivity occurred despite a simultaneous plasma oxypurinol concentration within recommended levels (below 100 mumol/l).