A New Variant of Glycogen Storage Disease Type I::Probably Due to a Defect in the Glucose-6-phosphate Transport System

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Glycogen storage disease Type I, which is called von Gierke's disease, are now divided in two groups. The most patients with Type I show an absence of glucose-6-phosphatase (G6Pase) in liver specimens biopsied (Type Ia). A few patients who are indistinguishable from Type I in clinical symptoms and biochemical findings reveal normal activity of hepatic G6Pase (Type Ib). The defect in Type Ib are unknown. But the accumulation of hepatic glycogen, poor response of blood glucose to glucagon and the result of glycerol loading test in such patients suggest that G6Pase demonstrated in vitro is not functional in vivo. A new variant of Type I glycogen storage disease which is probably due to a defect in G6P transport system is described. The patient Y. S. was born in 1975 and a girl of healthy, unrelated parents. The pregnancy and delivery were uneventful. She showed frequent episodes of hypoglycemia at fasting and consequently growth was retarded. At the age of 10 months, the patient showed all the features of glycogen storage disease Type I, such as hepatomegaly, growth retardation, doll-like appearance and rapid development of hypoglycemia after only 2 hours fasting, no response to glucagon, and a failure of the blood glucose to rise in response to administered galactose or fructose. Liver biopsy demonstrated an accumulation of glycogen (8.5% of wet weight) with normal structure. Enzyme analysis in the liver specimen, stored at -25° after its collection, revealed normal activities of glucose-6-phosphatase (4.5μmoles/min./g. liver) and fructose diphosphatase. Therefore, the patient was diagnosed as glycogen storage disease Type Ib. This studies were performed, with use of liver specimen obtained at the operation of mesenterico-caval shunt at the age of 3 years. Liver specimens immediately after biopsies were homogenized with 0.25M sucrose solution and centrifuged to remove nuclei and cellular debris. The supernatants were divided in two portions: one is treated with neutral deoxycholate (final, 0.2%) for two hours in cold to destroy microsomal membrane and the other is supplemented with distilled water, as described by Nordlie. G6P phosphohydrolase activities were measured in the homogenates with or without deoxycholate according to the procedure of Nordlie and Anon. The activity in the patient Y. S. was found to be markedly low (0.8μmoles/g. liver) as compared with those in control subjects and rats, when the assays were made in the absence of deoxycholate. However, the treatment of liver homogenates with detergent produced a restoration of the activity up to normal in the patient Y. S.(10.2μmoles/g. liver). The results from patients Y. S. suggest that a sufficient activity of G6Pase presents in microsomes of the liver but must be masked in intact microsomes, probably also in vivo as judged by the clinical and laboratory findings. The masking phenomenon observed in intact microsomes of the patient Y. S. can be explained by a lack of the G6P transport system, because the treatment with detergent brought the restoration of G6Pase activity. Our earlier observation, that the activity of hepatic G6Pase in patient Y. S. was normal, may be explained by a decrease in the latency of the enzyme during the storage at-25° which may destroy microsomal membranes. In fact, we have observed a decrease in the latency of mannose-6- phosphate phosphohydrolase, which is thought to be an index of microsomal integrity by freezing the liver specimens. This variant could be diagnosed only when the enzyme assay was carried out using both intact and disrupted preparation of microsomes.
Japan Society of Clinical Chemistryの論文

A New Variant of Glycogen Storage Disease Type I::Probably Due to a Defect in the Glucose-6-phosphate Transport System

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