Abstract
BackgroundPompe’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.MethodsFor 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 PPARα genes).We compared the polymorphisms analyzed in groups of patients with Pompe disease clustered for their homogeneous genotype.ResultsWe 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.ConclusionsWe demonstrate that ACE and ACTN3 polymorphisms are genetic factors able to modulate the clinical phenotype of patients affected with Pompe disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0102-z) contains supplementary material, which is available to authorized users.
Highlights
Pompe’s disease is a progressive myopathy caused by mutations in the lysosomal enzyme acid alphaglucosidase gene (GAA)
We collected the following data: age of onset of the disease, disease free survival is the time from birth to the age of symptom onset; presence or absence of muscular pain at any time after the diagnosis; Walton score [19]; 6-Minute Walking Test (6MWT) [20]; Vital Capacity, as expressed as percentage of decrease compared to controls (VC%); creatine kinase (CK)
No difference was found for age, gender and disease duration for any of the different subgroups identified by the polymorphisms studied for any gene; we report only details about Angiotensin converting enzyme (ACE) and actinin 3 (ACTN3) as they are the only genes whose polymorphisms showed some significant differences
Summary
Pompe’s disease is a progressive myopathy caused by mutations in the lysosomal enzyme acid alphaglucosidase gene (GAA). A wide clinical variability occurs in patients sharing the same GAA mutations, even within the same family. Glycogen Storage Disease type II (GSDII) or Pompe disease (OMIM 232300) is a lysosomal storage disorder caused by mutations in the acid alpha-glucosidase (GAA) gene whose frequency is about 1 in 40000–50000 in European and US Populations and apparently much lower in Australia or Portugal [1]. The same mutation can be observed in both infantile and late onset patients even if with different incidence; for instance, in two different groups of Italian patients, the c.525delT was observed in 13,8% in cases with the infantile form [9] and in 3,8% of cases of late onset disease [10]. A possible exception is the c.-32-13T > G mutation which never occurs in patients with the classic infantile form The same authors reported an incidence of 3,4% for the c.2237G > A mutation in infants as compared to an incidence of 10,3% in adults.
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