Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset Type II Glycogenosis?

Sabrina Ravaglia, Paola De Filippi, Anna Pichiecchio, Michela Ponzio, Kolsoum Saeidi Garaghani, Guy Umberto Poloni, Paola Bini, Cesare Danesino

Research output: Contribution to journalArticle


The purpose of this study is to analyze the role of genes known to influence muscle performances on the outcome after enzyme replacement treatment (ERT) in type II Glycogenosis (GSDII). We analyzed 16 patients receiving ERT for ≥ two years. We assessed the changes in muscle strength by hand-held dynamometry, muscle mass by quantitative MRI, and resistance to exercise by the 6-minute walking test. Exercise gene assessment included angiotensin converting enzyme insertion/deletion polymorphism (ACE), alpha-actinin3 R577X polymorphism (ACTN3), and peroxisome proliferator activated receptor alpha G/C polymorphism (PPARα). Independent of disease severity, one third of patients had a poor response to ERT, which was found to be associated with ACE DD genotype. The ACTN3 null polymorphism appeared to exert a positive effect on treatment efficacy, while PPARα did not seem to exert any influence at all. We conclude that poor treatment outcome in ACE DD genotypes is in line with previous observation of a worse disease course in this subpopulation, and suggests the need for a more careful follow-up and individualized treatment approaches for these patients. Exercise genes may provide a new opportunity for studying the outcome after treatment and the muscle regeneration abilities in other models of genetic myopathies.

Original languageEnglish
Pages (from-to)104-110
Number of pages7
JournalMolecular Genetics and Metabolism
Issue number1-2
Publication statusPublished - Sep 2012



  • Enzyme replacement therapy
  • Genetic polymorphisms
  • Glycogen storage disease type II
  • Volumetric MRI

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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