2,8-Dihydroxyadenine Lithiasis — Epidemiology, Pathogenesis and Therapy
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.
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- 1.Simmonds HA, Van Acker KJ (1983) Adenine phosphoribosyltransferase deficiency: 2,8-Dihy -droxadenine lithiasis. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds). The Metabolic Basis of Inherited Disease, 5th edn. McGraw-Hill, New York, p 1144–1156Google Scholar
- 3.Nobori T, Yamanaka H, Kamatani N, Nishioka K, Mikanagi K (1985) The prevalence of metabolic disorders in Japan. Ped Res 19:767 .Google Scholar
- 4.Fujimori S, Akaoka I, Sakamoto K, Yamanaka H, Nishioka K, Kamatani N (1985) Common characteristics of mutant adenine phosphoribosyltransferase from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies. Hum Genet 71:171–176 .PubMedCrossRefGoogle Scholar
- 6.Chevet D,Le Pogamp P, Gie S, Gary J, Daudon M, Hamet M (1984) 2,8-dihydroxyadenine (2,8-DHA) urolithiasis in an adult -complete adenine phosphoribosyltransferase deficiency -family study. Kidney International 26:226Google Scholar
- 8.Asper R, Schmucki O (1982) Diagnostik und therapie der 2,8-dihydroxyadenine-lithiasis. In: Gasser G, Vahlensieck W (eds) Pathogenese und Klinik der Harnsteine 1X, Steinkopff, Darmstadt, p 274–282 .Google Scholar
- 10.Labhart A. Zurich 1985 (personal communication) .Google Scholar
- 11.Muller MM, Vienna 1985 (personal communication) .Google Scholar
- 12.Joost J, Innsbruck 1985 (personal communication) .Google Scholar
- 14.Morris GS, Simmonds HA (1985) Use of a fundamental elution protocol for the development of a reverse phase HPLC method enabling rapid simultaneous determination of purines, pyrimidines and allied compounds commonly found in biological fluids. J Chromatog 344:101–133 .Google Scholar
- 15.Stenzel A, Ban -holzer P, Reiter S, Grobner W, Zollner N, Hegeman M, Pfab R (1985) Activity of adenine phosphoribosyltransferase (APRT) in patients with renal failure and urolithiasis. In: Schwille PO, Smith LH, Robertson WG, Vahlensieck W (eds) Urolithiasis and related clinical research. Plenum Press, New York, p 347–353 .CrossRefGoogle Scholar