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Glycogen storage disease type I: diagnosis and phenotype/genotype correlation.
Dietrich Matern1, Hans Hermann Seydewitz, Deeksha Bali
1Biochemical Genetics Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. matern@mayo.edu
European Journal of Pediatrics
|October 10, 2002
Summary
Glycogen storage disease type I (GSD I) encompasses genetically diverse subtypes. Molecular genetic analysis of G6PC and G6PT1 genes offers a reliable diagnostic alternative for GSD Ia and GSD I non-a, revealing numerous mutations.
Area of Science:
- Genetics
- Molecular Biology
- Pediatric Endocrinology
Background:
- Glycogen storage disease type Ia (GSD Ia) results from G6PC gene mutations, causing hepatomegaly, hypoglycemia, and metabolic derangements.
- GSD I non-a subtypes stem from G6PT1 gene mutations, often presenting with neutropenia and increased infection susceptibility.
- GSD I represents a spectrum of inherited metabolic disorders affecting glucose homeostasis.
Purpose of the Study:
- To conduct molecular genetic analyses of G6PC and G6PT1 genes in patients with GSD Ia and GSD I non-a.
- To identify and characterize mutations associated with different GSD I subtypes.
- To provide an overview of the molecular genetics of Glycogen Storage Disease Type I.
Main Methods:
- DNA sequencing of the G6PC gene in 130 GSD Ia patients.
- DNA sequencing of the G6PT1 gene in 15 GSD I non-a patients.
- Comprehensive literature review on GSD I molecular genetics.
Main Results:
- Identified 34 distinct mutations in the G6PC gene among GSD Ia patients, including two novel mutations (A65P; F177C).
- Detected 17 different mutations in the G6PT1 gene in GSD I non-a patients.
- No common mutations were found in either GSD Ia or GSD I non-a patient cohorts.
Conclusions:
- GSD Ia and GSD I non-a are genetically heterogeneous disorders.
- Molecular genetic analysis is a dependable and practical diagnostic method for GSD I, supplanting liver biopsy enzyme assays.
- Specific genotype-phenotype correlations were observed, including associations between G6PC mutations (G188R, 727G>T) and distinct clinical presentations or risks.