Abstract
McArdle’s disease, a glycogen storage disease type V, is caused by a deficiency of the enzyme myophosphorylase, encoded by the PYGM gene. Worldwide distribution of mutations has revealed interesting data about the prevalence of mutations and population migrations. Currently, more than 100 mutations in the PYGM gene have been described, with some recurrent mutations in the different populations. However, no molecular studies of McArdle’s disease were reported in Brazilian patients. Here, we describe the clinical phenotype and genotype of 10 patients from 8 unrelated Brazilian families. Among the 10 patients (3 females, 7 males), eight presented with the typical phenotype, with exercise intolerance, cramps, and myalgia; one patient showed permanent muscle weakness; and one patient showed a mild phenotype. Molecular analysis identified 5 different mutations in the 8 families, both in homozygosis or compound heterozygosis state. Four of them had already been described (p.R50X, p.T692kfs30, p.K609K, and p.G455R), and one, pI513V, is a novel heterozygous mutation. The common nonsense p.R50X mutation was found in 6 of the 8 families, being therefore the commonest mutation in the Brazilian population as well. Other mutations previously reported in European patients were also found in the patients in this study, which was expected considering the European ancestry of the Brazilian population.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andreu, A. L., Nogales-Gadea, G., Cassandrini, D., Arenas, C., & Bruno, C. (2007). McArdle disease: Molecular genotype update. Acta Myologica, XXVI, 53–57.
Arenas, J., Martin, M. A., Andreu, A. L. (2009). Glycogen storage disease type V. In GeneReviews at GeneTests: Medical genetics information resource (database online). Seattle: University of Washington, http://www.genetests.org.
Deschauer, M., Morgenroth, A., Joshi, P. R., et al. (2007). Analysis of spectrum and frequencies of mutations in McArdle disease. Journal of Neurology, 254, 797–802.
Fernandez- Cadenas, I., Andreu, A. L., et al. (2003). Splicing mosaico myophosphorylase gene due to a silent mutation in McArdle disease. Neurology, 61, 1432–1434.
García-Consuegra, I., Rubio, J. C., Nogales-Gadea, G., et al. (2009). Novel mutations in patients with McArdle disease by analysis of skeletal muscle mRNA. Journal of Medical Genetics, 46, 198–202.
Kararup, C. (1999). Pitfalls in electrodiagnosis. Journal of Neurology, 46(12), 1115–1126.
Lucia, A., Ruiz, J. R., Santalla, A., et al. (2012). Genotypic and phenotypic features of McArdle disease: Insights from the Spanish national registry. Journal of Neurology, Neurosurgery and Psychiatry, 83(3), 322–328.
Martin, M. A., Rubio, J. C., Buchbinder, J., et al. (2001). Molecular heterogeneity of myophosphorylase deficiency (McArdle′s disease): A genotype-phenotype correlation study. Annals of Neurology, 50, 574–581.
Pena, S. D., Pietro, G. D., Fuchshuber-Moraes, M., et al. (2011). The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected. PLoS ONE, 6, e17063.
Pérez, M., Foster, C., González-Freire, M., Arenas, J., & Lucia, A. (2007). One-year follow-up in a child with McArdle disease: Exercise is medicine. Pediatric Neurology, 38(2), 133–137.
Quintans, B., Sanchez- Andrade, A., Teijeira, S., et al. (2004). A new rare mutation (691del CC/insAA) in exon 17 of the PYGM gene causing McArdle disease. Archives of Neurology, 61, 1108–1110.
Rubio, J. C., Garcia-Consuegra, I., Nogales-Gadea, G., et al. (2007). A proposed molecular diagnostic flowchart for myophosphorylase deficiency (McArdle Disease) in blood samples from Spanish patients. Human Mutation, 28, 203–204.
Vieitz, I., Teijeira, S., Fernandez, J. M., et al. (2011). Molecular and clinical study of McArdle′s disease in a cohort of 123 European patients. Identification of 20 novel mutations. Neuromuscular Disorders, 21, 817–823.
Vissing, J., Duno, M., Scwartz, M., & Haller, R. (2009). Splice mutations preserve myophosphorylase activity that ameliorates the phenotype in Mc Ardle disease. Brain, 132, 1545–1552.
Acknowledgments
The authors would like to thank the following researchers, for scientific and technical support: Dr. Mayana Zatz, Dr. Lydia Yamamoto, Marta Canovas, and to Priscila Calyjur for English revision. Fapemig/Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais, FAPESP - Fundação de Amparo à pesquisa do estados de SP, CNPq INCT, FINEP.
Conflict of interest
There is no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gurgel-Giannetti, J., Nogales-Gadea, G., van der Linden, H. et al. Clinical and Molecular Characterization of Mcardle’s Disease in Brazilian Patients. Neuromol Med 15, 470–475 (2013). https://doi.org/10.1007/s12017-013-8233-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12017-013-8233-2