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)