Abstract
The use of oral adenine to prevent the devastating neurologic consequences of the Lesch-Nyhan syndrome has a sound theoretical basis, and has been proposed for management of this aspect of the disease. We have attempted therapy of two patients with adenine begun in one patient, during the first month of life. Preliminary experiments in rats explored the toxicity of adenine; pretreatment with allopurinol (10 mg/kg) reduced the nephrotoxic effects of the insoluble adenine metabolite, 2,8-dioxyadenine, at adenine doses of 70 mg/kg. Two patients, a 13-year-old male with established neurologic disease and self-mutilation, and a normal-appearing one-month-old boy with documented hypoxanthine-guanine phophoribosyltransferase (PRT) deficiency, were given adenine in doses up to 65 mg/kg/day. Toxicity was monitored by daily estimations of dioxyadenine content of urinary sediment and close attention ot parameters of renal functon; in both patients toxicity necessitated reduction in dose or addition of allopurinol. Erythrocyte 5-phosphori-bosyl-l-pyrophosphate which was normally elevated (40–70 mμmol/ml) as a consequence of PRT deficiency in these patients, was reduced to 5–15 mμmol/ml during adenine treatment, but not to within the normal range (1–5 mμmol/ml). The high uric acid excretion in both was unchanged. Despite treatment of the younger child for seven months, he developed spasticity, motor retardation and early self-mutilation. The older child alos showed no improvement in neurologic dysfunction. We conclude that adenine is of no therapeutic benefit, and is potentially toxic, in treatment of patients with the Lesch-Nyhan Syndrome.
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Schulman, J., Greene, M., Fujimoto, W. et al. Evaluation of Adenine Therapy for Lesch-Nyhan Syndrome. Pediatr Res 4, 452–453 (1970). https://doi.org/10.1203/00006450-197009000-00075
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DOI: https://doi.org/10.1203/00006450-197009000-00075
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