Genes and exercise intolerance: Insights from McArdle disease

Gisela Nogales-Gadea, Richard Godfrey, Alfredo Santalla, Jaume Coll-Cantí, Guillem Pintos-Morell, Tomàs Pinós, Joaquín Arenas, Miguel Angel Martín, Alejandro Lucia

Research output: Contribution to journalReview articleResearchpeer-review

13 Citations (Scopus)


© 2016 the American Physiological Society. 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 phosphor- ylase, “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 medi- cine as well as in future research on genetics and exercise-related phenotypes.
Original languageEnglish
Pages (from-to)93-100
JournalPhysiological Genomics
Issue number2
Publication statusPublished - 1 Feb 2016


  • Exercise
  • Genomics
  • Glycogenosis type V
  • Myophosphorylase
  • Rhabdomyolysis


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