Abstract
Glycogen storage disease type 1a (GSD 1a) is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase). A variant (GSD 1b) is caused by a defect in the transport of glucose-6-phosphate (G6P) into the microsome and is associated with chronic neutropenia and neutrophil dysfunction. Mutually exclusive mutations in the G6Pase gene and the G6P transport gene establish GSD 1a and GSD 1b as independent molecular processes and are consistent with a multicomponent translocase catalytic model. A modified translocase/catalytic unit model based on biochemical data in a G6Pase knockout mouse has also been proposed for G6Pase catalysis. This model suggests coupling of G6Pase activity and G6P transport. A 5-mo-old girl with hypoglycemia, hepatomegaly, and lactic acidemia was diagnosed with GSD 1a. She also developed neutropenia, neutrophil dysfunction, and recurrent infections characteristic of GSD 1b. Homozygous G188R mutations of the G6Pase gene were identified, but no mutations in the G6P translocase gene were found. We have subsequently identified a sibling and two unrelated patients with similar genotypic/phenotypic characteristics. The unusual association of neutrophil abnormalities in patients with homozygous G188R mutations in the G6Pase gene supports a modified translocase/catalytic unit model.
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Abbreviations
- GSD:
-
glycogen storage disease
- G6Pase:
-
glucose-6-phosphatase
- G6P:
-
glucose-6-phosphate
- PMN:
-
polymorphonuclear neutrophils
- PMA:
-
phorbol-myristate-acetate
- fMLP:
-
N-formyl-met-leu-phe
- SSCP:
-
single-strand conformation polymorphism
- G-CSF:
-
granulocyte-colony stimulating factor
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Acknowledgements
The authors thank Gerald Featherstone, Fernando DiMeo, and Dr. Hui Liu for their technical contributions.
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Supported in part by a grant from the National Institutes of Health, NIDDK #39078 (to Y.T.C.).
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Weston, B., Lin, JL., Muenzer, J. et al. Glucose-6-Phosphatase Mutation G188R Confers an Atypical Glycogen Storage Disease Type 1b Phenotype. Pediatr Res 48, 329–334 (2000). https://doi.org/10.1203/00006450-200009000-00011
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DOI: https://doi.org/10.1203/00006450-200009000-00011
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