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


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.


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.





glycogen debranching enzyme


glycogen storage disease


creatine kinase



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)


  1. Beauchamp NJ, Dalton A, Ramaswami U et al (2007) Glycogen storage disease type IX: high variability in clinical phenotype. Mol Genet Metab 92:88–99PubMedCrossRefGoogle Scholar
  2. Chen YT (2001) Chapter 71. Glycogen storage disease. In: Scriver C, Beaudet A, Sly W, Valle D et al (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw- Hill, New York, pp 1521–1551Google Scholar
  3. Endo Y, Horinishi A, Vorgerd M et al (2006) Molecular analysis of the AGL gene: heterogeneity of mutations in patients with glycogen storage disease type III from Germany, Canada, Afghanistan, Iran, and Turkey. J Hum Genet 51:958–963PubMedCrossRefGoogle Scholar
  4. Hers HG, Verhue W, Hoof V (1967) The determination of Amylo-1, 6-Glucosidase. Eur J Biochem 2:257–264PubMedCrossRefGoogle Scholar
  5. Horinishi A, Okubo M, Tang NL et al (2002) Mutational and haplotype analysis of AGL in patients with glycogen storage disease type III. J Hum Genet 47:55–59PubMedCrossRefGoogle Scholar
  6. Lucchiari S, Fogh I, Prelle A et al (2002) Clinical and genetic variability of glycogen storage disease type IIIa: seven novel AGL gene mutations in the Mediterranean Area. Am J Med Genet 109:183–190PubMedCrossRefGoogle Scholar
  7. Lucchiari S, Pagliarani S, Salani S et al (2006) Neuromuscular forms of glycogenosis Type III: nine mutations in AGL. Hum Mut; Mutation in brief, 897-(2006), onlineGoogle Scholar
  8. Okubo M, Horinishi A, Nakamura N et al (1998) A novel point mutation in an acceptor splice site of intron 32 (IVS32 A-12–>G) but no exon 3 mutations in the glycogen debranching enzyme gene in a homozygous patient with glycogen storage disease type IIIb. Hum Genet 102:1–5PubMedCrossRefGoogle Scholar
  9. Santer R, Tsiakas K, Bergmann J et al (2008) Molecular genetic diagnosis of glycogen storage disease (GSD) type III: experience from a large international cohort. J Inherit Metab Dis 31(Suppl 1):165Google Scholar
  10. Shaiu WL, Kishnani PS, Shen J et al (2000) Genotype-phenotype correlation in two frequent mutations and mutation update in type III glycogen storage disease. Mol Genet Metab 69:16–23PubMedCrossRefGoogle Scholar
  11. Shen JJ, Chen YT (2002) Molecular characterization of glycogen storage disease type III. Curr Mol Med 2:167–175PubMedCrossRefGoogle Scholar

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

Personalised recommendations