Study of Liver Metabolism in Glucose-6-Phosphatase Deficiency (Glycogen Storage Disease Type 1A) by P-31 Magnetic Resonance Spectroscopy

Abstract

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, glycerophosporylethanolamine), 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 rt 0.5, mean f 2 SD, n = 17). At the same time liver Pi was decreased in patients to 1.3 and 1.0, respectively (controls 1.8 f 0.8). Based on chemical shift measurements the increase in phosphomnnoesters 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-phosphatase-deficient patients during fasting. In these patients high levels may enhance the activity of residual glucose-6-phosphatase 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 Pi are known to regulate synthesis and breakdown purines. The changes in liver Pi during fasting and refeeding in these patients may stimulate production of uric acid and contribute to the hyperuricemia. (Pediatr Res 23: 375-380,1988) Glucose-6-phosphatase is necessary for the release of free glucose from glucose-6-P derived from glycogenolysis or gluconeogenesis. The link between glucose-6-phosphatase deficiency and its metabolic manifestations is not clear (1). Fasting hypoglycemia, a typical feature of glucose-6-phosphatase deficiency, can be accounted for by the block in glucose release. However, the striking ability of glucose-6-phosphatase-deficient patients to maintain from 30-100% of the normal glucose output during fasting has been difficult to explain in view of the reduction in hepatic glucose-6-phosphatase activity by more than 95% (2, 3) (Collins JE, Leonard JV, unpublished observations). A second clinical problem in glucose-6-phosphatase-deficient patients is hyperuricemia and gout (4-9). It has been suggested that the block in hepatic glucose release leads to accumulation of glucose-6-P during fasting. Glucose-6-P would overflow into the pentose phosphate shunt, increasing the formation of ribose-5-P and ultima...

Disturbed lipid metabolism in glycogen storage disease type 1

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Characterization of hepatic and brain metabolism in young adults with glycogen storage disease type 1: a magnetic resonance spectroscopy study

“…These divergent results could be due to limitations inherent to invasive tissue sampling (36,39). Nuclear magnetic resonance spectroscopy (NMRS) overcomes these limitations (33) and allows detection of increased hepatocellular concentrations of phosphomonoesters (PME) (28) and intrahepatocellular lipids (1). However, the PME peak derived from liver tissue contains the resonances of phosphorylated carbohydrates, including hexose, pentose, and triose phosphates as well as phosphocholine and phosphoethanolamine (12), and thus it has not yet been proven that the increased concentration of PME results from elevation of G6P.…”

Glucose production rates in type 1 glycogen storage disease

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