Glycogen Storage Disease Type 1b: Microsomal Glucose-6-Phosphatase System in Two Patients with Different Clinical Findings

Glycogen storage disease type 1a (von Gierke disease, GSD 1a) is caused by the deficiency of microsomal glucose-6-phosphatase (G6Pase) activity which catalyzes the final common step of glycogenolysis and gluconeogenesis. The recent cloning of the G6Pase cDNA and characterization of the human G6Pase gene enabled the characterization of the mutations causing GSD 1a. This, in turn, allows the introduction of a noninvasive DNA-based diagnosis that provides reliable carrier testing and prenatal diagnosis. In this study, we report the biochemical and clinical characteristics as well as mutational analyses of 12 Israeli GSD 1a patients of different families, who represent most GSD 1a patients in Israel. The mutations, G6Pase activity, and glycogen content of 7 of these patients were reported previously. The biochemical data and clinical findings of all patients were similar and compatible with those described in other reports. All 9 Jewish patients, as well as one Muslim Arab patient, presented the R83C mutation. Two Muslim Arab patients had the V166G mutation which was not found in other patients' populations. The V166G mutation, which was introduced into the G6Pase cDNA by site-directed mutagenesis following transient expression in COS-1 cells, was shown to cause complete inactivation of the G6Pase.The characterization of all GSD 1a mutations in the Israeli population lends itself to carrier testing in these families as well as to prenatal diagnosis, which was carried out in 2 families. Since all Ashkenazi Jewish patients harbor the same mutation, our study suggests that DNA-based diagnosis may be used as an initial diagnostic step in Ashkenazi Jews suspected of having GSD 1a, thereby avoiding liver biopsy. Am. J. Med. Genet. 72:286-290, 1997.

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“…G6Pase activity was assayed on fresh liver homogenate before and after disruption of microsomes as described previously [Narisawa et al, 1983].…”

Section: Methodsmentioning

confidence: 99%

Glycogen storage disease type 1a in Israel: Biochemical, clinical, and mutational studies

et al. 1997

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“…Kinetic anal ysis of G6P translocase with preparations from the adult patient was carried out. The apparent Km value was found to be about sixteen-fold higher than that of the controls [6]. This suggests that the residual activity of G6P translocase in patient Y.M.…”

Section: Systematic Microassay Methods For G6pase Systemmentioning

confidence: 74%

“…Using this systematic assay method for G6Pase system, additional 3 patients with GSD lb were examined [6,7,15], The G6P phosphohydrolase activity of the 'intact microsomes' was partially defi cient in Y.M., an adult with mild clinical symptoms, and undetectable in Yu.S. and Y.T., severely affected infants.…”

Section: Systematic Microassay Methods For G6pase Systemmentioning

confidence: 99%

“…From a technical point of view, the determination of the enzyme activities clini cally requires the use of methods which can be applied to small amounts of crude liver extracts. We developed micromethods to measure all three phosphohydrolase activi ties in both the untreated and the disrupted preparations, which can be applied to needle biopsy specimens [6].…”

Section: Systematic Microassay Methods For G6pase Systemmentioning

confidence: 99%

“…Y.M. [6,8] is a 25-year-old woman, who was diagnosed as GSD lb on the basis of laboratory analysis and G6Pase activity at the age of 20. Al though she has had subnormal fasting blood glucose concentrations, she did not present clinical evidence of hypoglycemia even during infancy or early child hood.…”

Section: Introductionmentioning

confidence: 99%

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Glycogen Storage Disease Type lb: Genetic Disorder Involving the Transport System of Intracellular Membrane

Narisawa

Igarashi²,

Tada³

1987

Enzyme

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Glycogen storage diseases (GSD) type lb is the first example of a genetic disorder involving the transport system of an intracellular membrane. It was revealed that the primary defect in GSD type lb was a deficiency in the microsomal glucose-6-phosphate (G6P) translocase, based on the findings that the glucose-6-phosphatase activity was highly latent in the fresh liver homogenates. Further evidence of this defect in GSD type lb has been provided by a membrane filter method which measures the uptake of ^14 UC-G6P by microsomes. The clinical symptoms and enzymatic studies in our patients suggest that there is genetic heterogeneity in GSD lb and the clinical severity depends on the level of residual activities of G6P translocase.

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Infectious and Bleeding Complications in Patients With Glycogenosis lb

Ambruso¹

1985

Arch Pediatr Adolesc Med

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Glycogen Storage Disease Type 1b: Microsomal Glucose-6-Phosphatase System in Two Patients with Different Clinical Findings

Cited by 37 publications

References 13 publications

Glycogen storage disease type 1a in Israel: Biochemical, clinical, and mutational studies

Glycogen storage disease type 1a in Israel: Biochemical, clinical, and mutational studies

Glycogen Storage Disease Type lb: Genetic Disorder Involving the Transport System of Intracellular Membrane

Infectious and Bleeding Complications in Patients With Glycogenosis lb

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