Oxypurine excretion,urinary xanthinuria

There were two subjects who clearly had primary xanthinuria (Table I), (Fig 1). P.J. and E.S. had 24-hour urinary excretion of uric acid of 36 and 19 mg/24 hr respectively and their serum uric acids were 1.1 and 0.7. After being on three days of a meat free diet their urinary uric acid values were 32 and 6.5 mg/24 hr, and their serum uric acid levels were 0.5 and 0.7 mg percent. In P.J. oxypurine excretion was unchanged by altering dietary urate being 409 and 407 mg/24 hr. In E.S. however oxypurine excretion fell from 263 mg/24 hr to 198 mg on a restricted diet. 

As close as can be calculated 36 of these should have been heterozygotes based on an autosomal recessive inheritance. It can be readily appreciated that in no case was an abnormality of serum or urinary uric acid perceived. Only one other patient besides our series was reportedly tested for increased urinary oxypurine and it was elevated. Tobias states in his review that oxypurine excretion was elevated in the children of two siblings with xanthinuria from Johannesburg although no data is available (5). Three of the 15 patients at risk in our kindred had elevated oxypurine on a low meat diet. 

The mode of inheritance of xanthinuria is one of the major concerns of this study. The fact that two siblings are involved and there is no vertical transmission make an autosomal recessive inheritance likely. Patient II3 could have been recessive with incomplete penetrance or a heterozygote. His son (III5) is almost certainly a heterozygote with virtually the same expression as his father i.e. normal serum urate (6.0 mg percent), urinary urate (609 mg/24 hr) and elevated oxypurine excretion. This makes it likely that II3 is a heterozygote and is strong evidence that the heterozygote can be identified at least in some cases. 

At the present time, we just report some experimental results of a study on the mechanism of action of allopurinol (U-hydroxy-pyrazolo (3, -d ) pyrimidine) and thiopurinol k thiopyrazolo (3, d) pyrimidine) on de novo biosynthesis of uric acid. In this present work, we have compared effect of alio and thiopurinol on oxypurine (xanthine and hypoxanthine) urinary excretion with their rate of synthesis of ribonucleotides in vitro by erythrocyte hemolysate in some particular enzymatic deficiencies (hypoxanthine-guanine phosphoribosyltransferase HGPRT, adenine phosphoribosyl-transferase APRT and xanthinuria). 

Xanthinuria is characterized by a large urinary excretion of oxypurine (xanthine + hypoxanthine) which replaces uric acid at the end product of purine metabolism. Patients with xanthinuria are very deficient in xanthine oxidase activity. This rare metabolic disorder may be of interest for both information ... 

---