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Journal of Inherited Metabolic Disease

, Volume 33, Supplement 3, pp 215–218 | Cite as

Glycogen storage disease type III in the Irish population

  • Ellen Crushell
  • Eileen P. Treacy
  • J. Dawe
  • M. Durkie
  • Nicholas J. Beauchamp
Research Report

Abstract

Glycogen storage disease type III (GSD III) results from mutations of the AGL gene encoding the glycogen debrancher enzyme. The disease has clinical and biochemical heterogeneity reflecting the severity of the AGL mutations. We sought to characterise the molecular defects in our cohort of Irish patients with GSD III. Fifteen patients from eight unrelated Irish families were identified: six males and nine females. The age ranged from 2–39 years old, and all presented in the first 3 years of life. Four patients (of three families) had mild disease with hepatomegaly, mild hypoglycaemia and normal creatine kinase (CK) levels. Five families had more severe disease, with liver and skeletal muscle involvement and elevated CK. Eleven different mutations were identified amongst the eight families. Of the 11, six were novel: p.T512fs, p.S736fs, p.A1400fs, p.K1407fs, p.Y519X and p.D627Y. The family homozygous for p.A1400fs had the most severe phenotype (early-onset hypoglycaemia, massive hepatomegaly, myopathy and hypertrophic cardiomyopathy before age 2 years), which was not halted by aggressive carbohydrate and protein supplementation. Conversely, the only missense mutation identified in the cohort, p.D627Y, was associated with a mild phenotype. The phenotypic diversity in our GSD III cohort is mirrored by the allelic heterogeneity. We describe two novel null mutations in exon 32 in two families with severe GSD III resistant to current treatment modalities. Knowledge of the specific mutations segregating in this cohort may allow for the development of new therapeutic interventions.

Keywords

Creatine Kinase Glycogen Storage Disease Type Elevated Creatine Kinase Mild Hypoglycaemia Skeletal Muscle Involvement 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AGL

amylo-1,6-glucosidase

GDE

glycogen debranching enzyme

GSD

glycogen storage disease

CK

creatine kinase

Notes

Acknowledgements

Dr. Charles O’Neill at the Department of Pathology, Children’s University Hospital, Dublin, Ireland, and Dr. Deeksha Bali at the Biochemical Genetics Laboratory, Duke University, NC, USA, for their assistance with mutation analysis.

Supplementary material

10545_2010_9096_MOESM1_ESM.doc (82 kb)
Table S1 (DOC 81 kb)

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Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Ellen Crushell
    • 1
  • Eileen P. Treacy
    • 1
  • J. Dawe
    • 2
  • M. Durkie
    • 2
  • Nicholas J. Beauchamp
    • 2
  1. 1.National Centre for Inherited Metabolic DisordersChildren’s University HospitalDublin 1Ireland
  2. 2.Sheffield Molecular Genetics ServiceSheffield Children’s NHS Foundation TrustSheffieldUK

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