Purine Excretion in Complete Adenine Phosphoribosyltransferase Deficiency: Effect of Diet and Allopurinol Therapy
Partial adenine phosphoribosyltransferase (APRTase) deficiency has been considered hitherto as relatively benign in that the only detectable abnormality of purine metabolism has been hyperuricaemia varyingly accompanied by hyperuricosuria in some, but not all, cases (3). Elsewhere in this symposium we present clinical details of a child apparently homozygous for APRTase deficiency with urolithiasis due to 2,8-dihydroxyadenine stone formation (11). An identical case of complete APRTase deficiency with 2,8-dihydroxy-adenine stone formation has been described by Cartier and Hamet (2). In both cases the stones were originally misdiagnosed as uric acid because of the non-specificity of the methods routinely used (2,8). The metabolic basis for the stone formation results directly from the enzyme deficiency. In the absence of APRTase adenine is oxidised to the extremely insoluble purine 2,8-dihydroxyadenine. The nephrotoxicity of 2,8-dihydroxyadenine has been known since 1898 and is discussed by Cameron et al. However, free adenine is not normally readily detectable in man, and the pathway for its production via adenosine and nucleoside Phosphorylase has very low activity in mammalian tissues (9,5). On this basis, endogenous adenine production would appear unlikely in normal circumstances.
KeywordsUric Acid Control Child Purine Metabolism Purine Nucleoside Phosphorylase Urinary Uric Acid
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