2,8-Dihydroxyadenine Lithiasis — Epidemiology, Pathogenesis and Therapy

Summary

2,8-dihydroxyadenine (2,8-DHA) is the insoluble purine responsible for a potentially lethal form of kidney stones, previously mistaken for uric acid in non-specific routine tests. Unlike uric acid the stones crush easily and do not react with uricase. The biochemical basis for 2,8-DHA lithiasis, a complete deficiency of the enzyme adenine phosphoribosyltransferase (APRT), has been found in 29 subjects from 11 countries, 20% of whom have been totally asymptomatic. An equal number presented in acute renal failure, 3 of whom are now on dialysis. Formation of 2,8 DHA can be prevented by allopurinol. This underlines the importance of early diagnosis, since such severe renal damage should be preventable. The number of stone-formers in Japan (10 homozygotes, 16 heterozygotes) Austria (3), and Switzerland (2) suggests more efficient diagnosis in those countries. Heterozygotes are normally asymptomatic. The defective enzyme in heterozygote stone-formers in Japan is a kinetic mutant demonstrable only in intact cells. The incidence of heterozygosity is approximately 1%, suggesting homozygosity may be more prevalent than is recognised. Whether juvenile gout may also be an accompaniment of partial APRT deficiency remains to be proven.