Diagnosis of type 1B and 1C glycogen storage disease

Burchell, Ann; Gibb, L

doi:10.1007/bf01811688

Cited by 23 publications

(11 citation statements)

References 6 publications

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“…Since this publication, GSD type Ic has been diagnosed in other cases, based on abnormal latency of G6Pase and inorganic pyrophosphatase in liver microsomes [245,[248][249][250]. Clinically, these cases do not seem to be distinguishable from GSD type Ib, although no systematic study has been published.…”

Section: Other Forms Of Gsd Type I ?mentioning

confidence: 99%

The glucose-6-phosphatase system

Schaftingen¹,

Gerin²

2002

Biochemical Journal

318

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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Section: Other Forms Of Gsd Type I ?mentioning

confidence: 99%

The glucose-6-phosphatase system

Schaftingen¹,

Gerin²

2002

Biochemical Journal

318

205

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“…In GSD 1c, but not in GSD 1b, the enzyme latency in isolated microsomes decreases with increasing G-6-P concentration. Furthermore, in intact microsomes enzyme activity is not detected when PPi is used as substrate while PPi is readily hydrolysed in disrupted microsomes (Burchell and Gibb 1991).…”

Section: Introductionmentioning

confidence: 99%

Molecular diagnosis of type 1c glycogen storage disease

et al. 1999

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Glycogen storage disease type 1 (GSD 1) results from deficiency of the microsomal multicomponent glucose-6-phosphatase system. Malfunction of the catalytic subunit characterises GSD 1a. GSD 1b and GSD 1c are characterised by defective microsomal glucose-6-phosphate or pyrophosphate/phosphate transport, respectively. Recently, a gene encoding a microsomal transporter protein has been found to be mutated in GSD 1b and 1c patients. Here, we report the genomic sequence of the transporter gene and the detection of a homozygous 2-bp deletion (1211delCT) and a homozygous donor splice site mutation (317+1G-->T) in two GSD 1c patients, confirming that GSD 1c is allelic to GSD 1b.

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“…In previous patients, where PPi transport has been essentially completely deficient (type lc a GSD), activity with G6P as substrate in intact microsomes has had a significantly increased K m and a relatively normal V x, presumably owing to the decreased rate of Pi release from the microsomes (Pi is a competitive inhibitor of the G6Pase enzyme) (Burchell and Gibb 1991;Nordlie et al 1992;Pears et al 1992). This was clearly not the case with this patient who in intact microsomes had a relatively normal K m but a very low Vax with G6P substrate (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Multiple transport protein defects in a patient with glycogen storage disease type 1: GSD 1b/1c_β

Hawkins

Kamath

Scott

et al. 1995

J of Inher Metab Disea

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A male child presented at 5 months of age with vomiting, diarrhoea, hypoglycaemia and hepatomegaly. Histology on a frozen liver biopsy suggested glycogen storage disease (GSD), while biochemical analyses confirmed an elevated glycogen content and normal activities of the GSD enzymes with the proviso that a variant of GSD 1 should be considered. The patient presented at 9 months of age with severe lactic acidosis and hypoglycaemia. A glucagon tolerance test and galactose load test on the patient produced no glycaemic response. A second biopsy was obtained and appropriately handled for the investigation of variants of the glucose-6-phosphatase enzyme (G6Pase) complex. Results showed that the patient had a deficiency of two transport proteins of the G6Pase complex, namely glucose-6-phosphate translocase and pyrophosphate translocase, i.e. GSD 1b/1c beta. These results were confirmed by additional kinetic analyses which provided confirmation of the double translocase deficiency. Evidence for inhibitors to these translocases was not found. The patient's treatment has resulted in the hypoglycaemia now being well controlled; however, at 3 years of age, height and weight are markedly lagging and he is moderately developmentally delayed. Neutropenia has not been found and neutrophil function is normal. Double enzyme deficiencies are very rare and possible explanations which might lead to this phenotype are considered. This, to the authors' knowledge, is the first report of a double translocase deficiency causing GSD type 1.

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Diagnosis of type 1B and 1C glycogen storage disease

Cited by 23 publications

References 6 publications

The glucose-6-phosphatase system

The glucose-6-phosphatase system

Molecular diagnosis of type 1c glycogen storage disease

Multiple transport protein defects in a patient with glycogen storage disease type 1: GSD 1b/1c_β

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Diagnosis of type 1B and 1C glycogen storage disease

Cited by 23 publications

References 6 publications

The glucose-6-phosphatase system

The glucose-6-phosphatase system

Molecular diagnosis of type 1c glycogen storage disease

Multiple transport protein defects in a patient with glycogen storage disease type 1: GSD 1b/1cβ

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Multiple transport protein defects in a patient with glycogen storage disease type 1: GSD 1b/1c_β