Journal of Inherited Metabolic Disease

, Volume 33, Supplement 3, pp 83–90 | Cite as

Glycogen storage disease type IV: novel mutations and molecular characterization of a heterogeneous disorder

  • Sing-Chung Li
  • Chiao-Ming Chen
  • Jennifer L. Goldstein
  • Jer-Yuarn Wu
  • Emmanuelle Lemyre
  • Thomas Andrew Burrow
  • Peter B. Kang
  • Yuan-Tsong Chen
  • Deeksha S. Bali
Research Report


Glycogen storage disease type IV (GSD IV; Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE), leading to excessive deposition of structurally abnormal, amylopectin-like glycogen in affected tissues. The accumulated glycogen lacks multiple branch points and thus has longer outer branches and poor solubility, causing irreversible tissue and organ damage. Although classic GSD IV presents with early onset of hepatosplenomegaly with progressive liver cirrhosis, GSD IV exhibits extensive clinical heterogeneity with respect to age at onset and variability in pattern and extent of organ and tissue involvement. With the advent of cloning and determination of the genomic structure of the human GBE gene (GBE1), molecular analysis and characterization of underlying disease-causing mutations is now possible. A variety of disease-causing mutations have been identified in the GBE1 gene in GSD IV patients, many of whom presented with diverse clinical phenotypes. Detailed biochemical and genetic analyses of three unrelated patients suspected to have GSD IV are presented here. Two novel missense mutations (p.Met495Thr and p.Pro552Leu) and a novel 1-bp deletion mutation (c.1999delA) were identified. A variety of mutations in GBE1 have been previously reported, including missense and nonsense mutations, nucleotide deletions and insertions, and donor and acceptor splice-site mutations. Mutation analysis is useful in confirming the diagnosis of GSD IV—especially when higher residual GBE enzyme activity levels are seen and enzyme analysis is not definitive—and allows for further determination of potential genotype/phenotype correlations in this disease.



Adult polyglucosan body disease


Fetal akinesia deformation sequence


Glycogen branching enzyme 1


Glycogen storage disease type IV (Andersen disease)



We acknowledge Denise Peterson for her technical support in evaluating enzyme levels on these patients. We are also grateful to the GSD IV patient population for their willingness to participate in this study.


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Copyright information

© SSIEM and Springer-Verlag 2009

Authors and Affiliations

  • Sing-Chung Li
    • 1
    • 2
  • Chiao-Ming Chen
    • 1
    • 2
  • Jennifer L. Goldstein
    • 7
  • Jer-Yuarn Wu
    • 3
  • Emmanuelle Lemyre
    • 4
  • Thomas Andrew Burrow
    • 5
  • Peter B. Kang
    • 6
  • Yuan-Tsong Chen
    • 3
  • Deeksha S. Bali
    • 7
  1. 1.School of Nutrition and Health ScienceTaipei Medical UniversityTaipeiTaiwan
  2. 2.Department of Food Science, Nutrition and Nutraceutical BiotechnologyShih Chien UniversityTaipeiTaiwan
  3. 3.Institute of Biomedical ScienceAcademia SinicaTaipeiTaiwan
  4. 4.Saint-Justine HospitalMontrealCanada
  5. 5.Cincinnati Children’s Hospital Medical CenterCincinnatiUSA
  6. 6.Children′s Hospital Boston and Harvard Medical SchoolBostonUSA
  7. 7.Pediatrics, Biochemical Genetics LaboratoryDuke University Medical CenterDurhamUSA

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