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Glycogen storage disease type I: diagnosis and phenotype/genotype correlation

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Abstract

Glycogen storage disease type Ia (GSD Ia) is caused by mutations in theG6PC gene encoding the phosphatase of the microsomal glucose-6-phosphatase system. GSD Ia is characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia and short stature. Other forms of GSD I (GSD I non-a) are characterized by the additional symptom of frequent infections caused by neutropenia and neutrophil dysfunction. GSD I non-a is caused by mutations in a gene encoding glucose-6-phosphatase translocase (G6PT1). We report on the molecular genetic analyses of G6PC and G6PT 1 in 130 GSD Ia patients and 15 GSD I non-a patients, respectively, and provide an overview of the current literature pertaining to the molecular genetics of GSD I. Among the GSD Ia patients, 34 different mutations were identified, two of which have not been described before (A65P; F117C). Seventeen different mutations were detected in the GSD I non-a patients. True common mutations were identified neither in GSD Ia nor in GSD I non-a patients,Conclusion: Glycogen storage disease type Ia and and type I non-a are genetically heterogenous disorders. For the diagnosis of the various forms of glycogen storage disease type I, molecular genetic analyses are reliable and convenient alternatives to the enzyme assays in liver biopsy specimens. Some genotype-phenotype correlations exist, for example, homozygosity for oneG6PC mutation, G188R, seems to be associated with a glycogen storage disease type I non-a phenotype and homozygosity for the 727G>T mutation may be associated with a milder phenotype but an increased risk for hepatocellular carcinoma.

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Abbreviations

GSD :

glycogen storage disease

G6Pase :

glucose-6-phosphatase

HCC :

hepatocellular carcinoma

SSCP :

single-strand conformation polymorphism

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Authors and Affiliations

  1. Biochemical Genetics Laboratory, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA

    Dietrich Matern

  2. Children’s Hospital, Albert-Ludwigs-University, Freiburg, Germany

    Hans Hermann Seydewitz & Christine Lang

  3. Department of Pediatrics, Duke University Medical Center, Durham, NC, USA

    Deeksha Bali & Yuan-Tsong Chen

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  1. Dietrich Matern
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  2. Hans Hermann Seydewitz
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  3. Deeksha Bali
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  4. Christine Lang
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  5. Yuan-Tsong Chen
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Correspondence to Dietrich Matern.

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Published online: 27 July 2002

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Matern, D., Seydewitz, H.H., Bali, D. et al. Glycogen storage disease type I: diagnosis and phenotype/genotype correlation. Eur J Pediatr 161, S10–S19 (2002). https://doi.org/10.1007/BF02679989

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