2,8-Dihydroxyadenine lithiasis

Abstract

2,8-Dihydroxyadenine (2,8-DHA) lithiasis is a form of kidney stone previously mistaken for uric acid because of identical reactivity in non-specific tests used routinely in stone analysis. Unlike uric acid, the stones crush easily and do not react with uricase. The biochemical basis for the defect is a deficiency of the enzyme adenine phosphoribosyltransferase (APRT). A complete deficiency has been reported in 29 patients from 11 countries. The number of stone formers reported in Japan (10 homozygotes, 16 heterozygotes) Austria (3), and Switzerland (2) suggests more efficient diagnosis in those countries. The defective enzyme in heterozygotes in Japan is a kinetic mutant demonstrable in intact not lysed cells. 20% of APRT-deficient subjects have been asymptomatic. An equal number have presented in acute renal failure, three of whom are now on dialysis. Formation of the nephrotoxic 2,8-DHA can be prevented by allopurinol. This underlines the importance of early diagnosis, since such severe renal damage should be avoidable.