Acute Renal Failure During Adenine Therapy in Lesch-Nyhan Syndrome
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Additional adenine and folic acid are required for optimal growth of hypoxanthine-guaine phosphoribosyltransferase (HGPRT) deficient fibroblasts in tissue culture(1). On this ground adenine therapy was advised in Lesch-Nyhan (LN) syndrome and resulted in a prompt correction of megaloblastic anemia in two cases(2). In mammalian tissue adenine is easily converted into adenosine monophosphat by adenine phosphoribosyltransferase, utilizing 5-phosphoribosylpyrophosphate (PRPP). “Inappropriate” purine biosynthesis “de novo” in ln syndrome can be just accounted for an increased availability of PRPP due to missing competition between HGPRT and glutamine-PRPP-amidotransferase for this substrate(3–5). Consequently PRPP consumption from adenine is likely to result in a decreased purine biosynthesis, as proved by lesser incorporation of 14C-glycine in urinary uric acid (ua)(2). Nevertheless adenine therapy showed conflicting evidence of inhibiting purine biosynthesis, since a decrease of urinary ua was not evidenced in two cases in spite of a reduction of erythrocyte PRPP(6). Therefore we think that any further contribution on this topic is of some interest.
KeywordsMegaloblastic Anemia Spastic Cerebral Palsy Amniotic Fluid Cell Purine Biosynthesis Urinary Uric Acid
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