A Contribution of Hepatic Purine Degradation Induced by Hypoglycemia to the Development of Hyperuricemia in Glycogen Storage Disease Type I

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To elucidate the mechanism by which hyperuricemia develops in glycogen storage disease type I (GSD I), we studied seven patients with this disease. After an overnight fast hyproglycemia w a s associated with high plasma levels of oxypurines (hypoxanthine and xanthine). Administration of glucose(75g, p.o.) normalized these abnormalities as well as hyperglucagonemia, suggesting that hyproglycemia accelerates purine degradation in GSD I. Administration of either glucagon(lmg i.v.) or fructose(0.5g/kg body weight, p.o.) decreased the plasma inorganic phosphate level and increased the plasma oxypurine level, followed by elevation of serum uric acid levels. The urinary excretion of these purine metabolites were also increased. After maintaining normoglycemia by intravenous hyperalimentation therapy, hyperuricemia was cured. In addition,24-hour urinary excretion of uric acid was decreased, and the uric acid/creatinine clearance ratio was increased. Analyses of liver biopsy specimens from the patients revealed an incleased hexose monophosphate pool and low ATP levels accompanied by high AMP levels. These findings indicate that 1) not only decreased renal urate clearance but also enhanced hepatic purine degradation is responsible for the development of hyperuricemia in GSD I and 2)privention of hyproglycemia corrects these metabolic derangements.
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