Study of liver metabolism in glucose-6-phosphatase deficiency (glycogen storage disease type 1a) by p-31 magnetic resonance spectroscopy

Abstract

Liver metabolism of two patients (aged 15 and 23 yr) was studied by P-31 magnetic resonance spectroscopy at 1.9 tesla. The P-31 spectra of liver showed the resonances of phosphomonoesters (including sugar phosphates), inorganic phosphate (Pi), phosphodiesters (e.g. glycerophosphorylcholine, glycerophosporylethanol-amine), and ATP. These resonances were quantified by expressing their peak areas in mM (assuming that ATP concentrations in normal liver is 2.5 mM) or as a ratio relative to the area of the phosphodiester resonance. After an overnight fast liver phosphomonoesters in patients were 2.6 and 1.6 AU, respectively (controls 1.1 ± 0.5, mean ± 2 SD, n = 17). At the same time liver Pi was decreased in patients to 1.3 and 1.0, respectively (controls 1.8 ± 0.8). Based on chemical shift measurements the increase in phosphomonoesters could be attributed to accumulation of sugar phosphates (mainly glycolytic intermediates). After 1 g/kg oral glucose, hepatic sugar phosphates decreased in patients by 64 and 40%, respectively, and reached normal levels (on the absolute intensity scale); whereas liver Pi increased by 130 and 40%, respectively. Liver Pi levels remained elevated in both patients 30 min after ingestion of glucose. Liver sugar phosphates and Pi did not change in control subjects (n = 4) after glucose. In contrast to some previous reports, we have found accumulation of glycolytic intermediates in the liver of glucose-6-phospha-tase-deficient patients during fasting. In these patients high levels may enhance the activity of residual glucose-6-phos-phatase thus increasing hepatic glucose production and reducing the degree of hypoglycemia during fasting. Hyperuricemia is another serious complication of glucose-6-phosphatase deficiency and was present in both patients. Levels of Pj are known to regulate synthesis and breakdown purines. The changes in liver Pi during fasting and refeed-ing in these patients may stimulate production of uric acid and contribute to the hyperuricemia. © 1988 International Pediatric Research Foundation. Inc.