Glycogen storage disease type Ia: recent experience with mutation analysis, a summary of mutations reported in the literature and a newly developed diagnostic flowchart

Rake, Jan Peter; Berge, A ten; Visser, Gepke; Verlind, E; Niezen-Koning, Klaziena; Buys, Chcm; Smit, Gerrit; Scheffer, Hans

doi:10.1007/s004310051281

Cited by 59 publications

(54 citation statements)

References 42 publications

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“…GSD Ia is thus, as previously reported, genetically heterogeneous (Chevalier-Porst et al, 1996;Lei et al, 1995;Rake et al, 2000). Most patients are compound heterozygotes.…”

Section: Resultssupporting

confidence: 56%

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Genetic heterogeneity of glycogen storage disease type Ia in France: A study of 48 patients

et al. 2000

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Forty-eight patients with glycogen storage disease type Ia (GSD Ia) were studied. Using a combination of single-strand conformation polymorphism (SSCP) analysis, restriction enzyme digestion and direct sequencing, we were able to identify 93/96 mutant alleles, comprising 23 different mutations in the glucose-6-phosphatase gene (G6PC). Among these, 7 are novel mutations of G6PC: M5R, T111I, A241T, C270R, F322L, and two deletions, 793delG and 872delC, resulting in the same mutation at the amino acid level, fs300Ter (300X).

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“…GSD Ia is thus, as previously reported, genetically heterogeneous (Chevalier-Porst et al, 1996;Lei et al, 1995;Rake et al, 2000). Most patients are compound heterozygotes.…”

Section: Resultssupporting

confidence: 56%

“…Since the cloning of the gene encoding G6Pase (G6PC, GDB:231927), almost 60 mutations have been reported, thus illustrating the genetic heterogeneity of the disease (for review, see : Rake et al;2000). Here we report the identification of 93/96 mutant alleles in 48 patients with GSD Ia.…”

Section: Introductionmentioning

confidence: 91%

Genetic heterogeneity of glycogen storage disease type Ia in France: A study of 48 patients

et al. 2000

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“…The deficiency of G6Pase activity is caused by mutations in the gene encoding this enzyme [42,189,[225][226][227]. In their 1999 review paper [226], Chou and Mansfield mentioned 31 distinct mutations identified in a total of 128 patients.…”

Section: Gsd Type Iamentioning

confidence: 99%

The glucose-6-phosphatase system

Schaftingen¹,

Gerin²

2002

Biochemical Journal

322

205

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Glucose-6-phosphatase (G6Pase), an enzyme found mainly in the liver and the kidneys, plays the important role of providing glucose during starvation. Unlike most phosphatases acting on water-soluble compounds, it is a membrane-bound enzyme, being associated with the endoplasmic reticulum. In 1975, W. Arion and co-workers proposed a model according to which G6Pase was thought to be a rather unspecific phosphatase, with its catalytic site oriented towards the lumen of the endoplasmic reticulum [Arion, Wallin, Lange and Ballas (1975) Mol. Cell. Biochem. 6, 75–83]. Substrate would be provided to this enzyme by a translocase that is specific for glucose 6-phosphate, thereby accounting for the specificity of the phosphatase for glucose 6-phosphate in intact microsomes. Distinct transporters would allow inorganic phosphate and glucose to leave the vesicles. At variance with this substrate-transport model, other models propose that conformational changes play an important role in the properties of G6Pase. The last 10 years have witnessed important progress in our knowledge of the glucose 6-phosphate hydrolysis system. The genes encoding G6Pase and the glucose 6-phosphate translocase have been cloned and shown to be mutated in glycogen storage disease type Ia and type Ib respectively. The gene encoding a G6Pase-related protein, expressed specifically in pancreatic islets, has also been cloned. Specific potent inhibitors of G6Pase and of the glucose 6-phosphate translocase have been synthesized or isolated from micro-organisms. These as well as other findings support the model initially proposed by Arion. Much progress has also been made with regard to the regulation of the expression of G6Pase by insulin, glucocorticoids, cAMP and glucose.

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“…In this model, the combined activities of the G6P translocator and G6P phosphatase would concentrate glucose in the ER lumen, permitting an efficient second efflux route which would be active, allowing the export of glucose into the serum against a concentration gradient. As of yet, all cases of type I glycogen storage diseases are linked to defects in either the glucose-6-phosphatase or the G6P translocase gene, suggesting that mutations in glucose transport across the ER membrane are lethal or that ER transport systems are functionally redundant (28,30,35).…”

mentioning

confidence: 99%

Evidence for High-Capacity Bidirectional Glucose Transport across the Endoplasmic Reticulum Membrane by Genetically Encoded Fluorescence Resonance Energy Transfer Nanosensors

Fehr

Takanaga

Ehrhardt

et al. 2005

Molecular and Cellular Biology

104

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Glucose release from hepatocytes is important for maintenance of blood glucose levels. Glucose-6-phosphate phosphatase, catalyzing the final metabolic step of gluconeogenesis, faces the endoplasmic reticulum (ER) lumen. Thus, glucose produced in the ER has to be either exported from the ER into the cytosol before release into circulation or exported directly by a vesicular pathway. To measure ER transport of glucose, fluorescence resonance energy transfer-based nanosensors were targeted to the cytosol or the ER lumen of HepG2 cells. During perfusion with 5 mM glucose, cytosolic levels were maintained at ϳ80% of the external supply, indicating that plasma membrane transport exceeded the rate of glucose phosphorylation. Glucose levels and kinetics inside the ER were indistinguishable from cytosolic levels, suggesting rapid bidirectional glucose transport across the ER membrane. A dynamic model incorporating rapid bidirectional ER transport yields a very good fit with the observed kinetics. Plasma membrane and ER membrane glucose transport differed regarding sensitivity to cytochalasin B and showed different relative kinetics for galactose uptake and release, suggesting catalysis by distinct activities at the two membranes. The presence of a high-capacity glucose transport system on the ER membrane is consistent with the hypothesis that glucose export from hepatocytes occurs via the cytosol by a yet-to-be-identified set of proteins.

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Glycogen storage disease type Ia: recent experience with mutation analysis, a summary of mutations reported in the literature and a newly developed diagnostic flowchart

Abstract: Increased knowledge of the genetic basis of glycogen storage disease type I provides a DNA-based diagnosis, prenatal DNA-based diagnosis in chorionic villus samples and carrier detection.

Cited by 59 publications

References 42 publications

Genetic heterogeneity of glycogen storage disease type Ia in France: A study of 48 patients

Genetic heterogeneity of glycogen storage disease type Ia in France: A study of 48 patients

The glucose-6-phosphatase system

Evidence for High-Capacity Bidirectional Glucose Transport across the Endoplasmic Reticulum Membrane by Genetically Encoded Fluorescence Resonance Energy Transfer Nanosensors

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