title: Genes and exercise intolerance: insights from McArdle disease.
abstract: McArdle disease (glycogen storage disease type V) is caused by inherited deficiency of a key enzyme in muscle metabolism, the skeletal muscle-specific isoform of glycogen phosphorylase, "myophosphorylase," which is encoded by the PYGM gene. Here we review the main pathophysiological, genotypic, and phenotypic features of McArdle disease and their interactions. To date, moderate-intensity exercise (together with pre-exercise carbohydrate ingestion) is the only treatment option that has proven useful for these patients. Furthermore, regular physical activity attenuates the clinical severity of McArdle disease. This is quite remarkable for a monogenic disorder that consistently leads to the same metabolic defect at the muscle tissue level, that is, complete inability to use muscle glycogen stores. Further knowledge of this disorder would help patients and enhance understanding of exercise metabolism as well as exercise genomics. Indeed, McArdle disease is a paradigm of human exercise intolerance and PYGM genotyping should be included in the genetic analyses that might be applied in the coming personalized exercise medicine as well as in future research on genetics and exercise-related phenotypes.
authors.affiliation: Translational Research Laboratory in Neuromuscular Diseases, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol i Campus Can Ruti, Universitat Autònoma de Barcelona, Badalona, Spain; gnogalga7@gmail.com.
authors.forename: Gisela
authors.initials: G
authors.lastname: Nogales-Gadea
authors.affiliation: Centre for Sports Medicine and Human Performance, Brunel University, London, United Kingdom;
authors.forename: Richard
authors.initials: R
authors.lastname: Godfrey
authors.affiliation: Universidad Pablo de Olavide, Seville, Spain; Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain;
authors.forename: Alfredo
authors.initials: A
authors.lastname: Santalla
authors.affiliation: Translational Research Laboratory in Neuromuscular Diseases, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol i Campus Can Ruti, Universitat Autònoma de Barcelona, Badalona, Spain; Servicio de Neurología, Unidad Neuromuscular, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain;
authors.forename: Jaume
authors.initials: J
authors.lastname: Coll-Cantí
authors.affiliation: Translational Research Laboratory in Neuromuscular Diseases, Department of Neurosciences, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol i Campus Can Ruti, Universitat Autònoma de Barcelona, Badalona, Spain; Servicio de Pediatría, Unidad de Enfermedades Minoritarias, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Guillem
authors.initials: G
authors.lastname: Pintos-Morell
authors.affiliation: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Departament de Patologia Mitocondrial i Neuromuscular, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autónoma de Barcelona, Barcelona, Spain;
authors.forename: Tomàs
authors.initials: T
authors.lastname: Pinós
authors.affiliation: Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain; and.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.affiliation: Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital 12 de Octubre, Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain; and.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Martín
authors.affiliation: Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain; and Universidad Europea, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015444:Exercise; D017079:Exercise Tolerance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006003:Glycogen / Q000378:metabolism; D024982:Glycogen Phosphorylase, Muscle Form / Q000172:deficiency / Q000235:genetics; D006012:Glycogen Storage Disease Type V / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D012042:Registries; D013030:Spain
chemical_list: D006003:Glycogen; D024982:Glycogen Phosphorylase, Muscle Form
keywords: exercise; genomics; glycogenosis type V; myophosphorylase; rhabdomyolysis