Genotype-phenotype correlation in Pompe disease, a step forward

Paola De Filippi, Kolsoum Saeidi, Sabrina Ravaglia, Andrea Dardis, Corrado Angelini, Tiziana Mongini, Lucia Morandi, Maurizio Moggio, Antonio Di Muzio, Massimiliano Filosto, Bruno Bembi, Fabio Giannini, Giovanni Marrosu, Miriam Rigoldi, Paola Tonin, Serenella Servidei, Gabriele Siciliano, Annalisa Carlucci, Claudia Scotti, Mario ComelliAntonio Toscano, Cesare Danesino

Research output: Contribution to journalArticlepeer-review


Background: Pompe's disease is a progressive myopathy caused by mutations in the lysosomal enzyme acid alphaglucosidase gene (GAA). A wide clinical variability occurs also in patients sharing the same GAA mutations, even within the same family.

Methods. For a large series of GSDII patients we collected some clinical data as age of onset of the disease, presence or absence of muscular pain, Walton score, 6-Minute Walking Test, Vital Capacity, and Creatine Kinase. DNA was extracted and tested for GAA mutations and some genetic polymorphisms able to influence muscle properties (ACE, ACTN3, AGT and PPAR genes). We compared the polymorphisms analyzed in groups of patients with Pompe disease clustered for their homogeneous genotype.

Results: We have been able to identify four subgroups of patients completely homogeneous for their genotype, and two groups homogeneous as far as the second mutation is defined "very severe" or "potentially less severe". When disease free life was studied we observed a high significant difference between groups. The DD genotype in the ACE gene and the XX genotype in the ACTN3 gene were significantly associated to an earlier age of onset of the disease. The ACE DD genotype was also associated to the presence of muscle pain.

Conclusions: We demonstrate that ACE and ACTN3 polymorphisms are genetic factors able to modulate the clinical phenotype of patients affected with Pompe disease.

Original languageEnglish
Article number102
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - Aug 8 2014


  • ACE
  • ACTN3
  • GAA
  • Genetic polymorphisms
  • Glycogen storage disease type II
  • Modifier genes

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)


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