Adenine therapy in Lesch-Nyhan syndrome.
In a 7-year-old patient with Lesch-Nyhan syndrome (LNS) the 15N excess frequency was determined in the excreted uric acid after oral application of 27 mg 15N glycine/kg body weight, using emission spectrometry. Incorporation of glycine into uric acid was considerably increased in untreated LNS in comparison with the control. This was due to the extremely increased endogenous de novo synthesis of purine. Allopurinol therapy caused only a gradual decrease of uric acid excretion. The pattern of purine excretion changed in favour of the better soluble oxipurines hypoxanthine and xanthine, by competitive inhibition of xanthine oxidase. In LNS, however, allopurinol had no uricostatic effect. Therapy with adenine is an alternative to influence the de novo synthesis. After adenine application a decrease of the cumulative 15N uric acid excretion occurs and the percentual proportion of 15N uric acid in total 15N excretion decreases. These changes are due to an inhibition of de novo purine biosynthesis. Adenine, however, must be applied in combination with allopurinol in order to avoid the formation of nephrotoxic 2,8-dioxiadenine by xanthine oxidase. Adenine therapy led to an improvement of the clinical course. No side-effects were observed.
D000225:Adenine / Q000627:therapeutic use*; D000493:Allopurinol / Q000627:therapeutic use*; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D007926:Lesch-Nyhan Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
D011687:Purines; D014527:Uric Acid; D000493:Allopurinol; D007041:Hypoxanthine Phosphoribosyltransferase; D000225:Adenine