Muscle fiber-type distribution, fiber-type-specific damage, and the Pompe disease phenotype
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ORIGINAL ARTICLE
Muscle fiber-type distribution, fiber-type-specific damage, and the Pompe disease phenotype L. E. M. van den Berg & M. R. Drost & G. Schaart & J. de Laat & P. A. van Doorn & A. T. van der Ploeg & A. J. J. Reuser
Received: 21 June 2012 / Revised: 3 September 2012 / Accepted: 11 September 2012 # SSIEM and Springer Science+Business Media Dordrecht 2012
Abstract Pompe disease is a lysosomal storage disorder caused by acid α-glucosidase deficiency and characterized by progressive muscle weakness. Enzyme replacement therapy (ERT) has ameliorated patients’ perspectives, but reversal of skeletal muscle pathology remains a challenge. We studied pretreatment biopsies of 22 patients with different phenotypes to investigate to what extent fiber-type distribution and fiber-type-specific damage contribute to clinical diversity. Pompe patients have the same fiber-type distribution as healthy persons, but among nonclassic patients with the same GAA mutation (c.-32-13T>G), those with early onset of symptoms tend to have more type 2 muscle fibers Communicated by: Ed Wraith Electronic supplementary material The online version of this article (doi:10.1007/s10545-012-9541-7) contains supplementary material, which is available to authorized users. L. E. M. van den Berg : A. T. van der Ploeg Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands M. R. Drost : G. Schaart Department of Movement Sciences, School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, The Netherlands J. de Laat : A. J. J. Reuser (*) Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands e-mail: [email protected] P. A. van Doorn Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands
than those with late-onset disease. Further, it seemed that the older, more severely affected classic infantile patients and the wheelchair-bound and ventilated nonclassic patients had a greater proportion of type 2x muscle fibers. However, as in other diseases, this may be caused by physical inactivity of those patients.
Introduction Pompe disease (glycogen storage disease type II, acid maltase deficiency) (OMIM 232300) is an inherited lysosomal storage disorder caused by the deficiency of acid αglucosidase (EC 3.2.1.3). Deficiency of this lysosomal enzyme leads to glycogen accumulation in a variety of tissues, including skeletal muscle (Hirschorn and Reuser 2001; van der Ploeg et al. 2010). Pompe disease shows a broad clinical spectrum, ranging from the classic infantile form characterized by hypotonia, hypertrophic cardiomyopathy, and death within the first year of life (van den Hout et al. 2003; Kishnani et al. 2006), to more slowly progressive forms characterized by proximal muscle weakness and respiratory problems in c
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