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McArdle disease: what do neurologists need to know?


McArdle disease (also known as glycogen storage disease type V) is a pure myopathy caused by an inherited deficit of myophosphorylase, the skeletal muscle isoform of the enzyme glycogen phosphorylase. The disease exhibits clinical heterogeneity, but patients typically experience exercise intolerance, that is, reversible, acute crises (early fatigue and contractures, sometimes with rhabdomyolysis and myoglobinuria) triggered by static muscle contractions (e.g. lifting weights) or dynamic exercise (e.g. climbing stairs or running). In this Review, we discuss the main features of McArdle disease, with the aim of providing neurologists with up-to-date, useful information to assist their patients. The topics covered include diagnostic tools—for example, molecular genetic diagnosis, the classic ischemic forearm test and the so-called 'second wind' phenomenon—and current therapeutic options—for example, a carbohydrate-rich diet and carbohydrate ingestion shortly before strenuous exercise, in combination with medically supervised aerobic training of low to moderate intensity.

Key Points

  • McArdle disease is a pure myopathy caused by an inherited deficit of the skeletal muscle isoform of glycogen phosphorylase

  • The main problem in this condition is exercise intolerance, with most patients experiencing acute 'muscle crises' after static or intense dynamic exercise

  • Crises appear in the form of early muscle fatigue and contractures, sometimes with marked muscle breakdown (rhabdomyolysis) and myoglobinuria

  • Until a definitive cure is found, patients can benefit from adopting a diet rich in complex carbohydrates and ingesting simple carbohydrates before strenuous exercise

  • Carefully supervised, regular, aerobic exercise of low to moderate intensity is a safe, recommended therapeutic option, but exercises that involve heavy static contractions or induce severe myalgia should be avoided

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Figure 1: Schematic representation of skeletal muscle glycogen metabolism.


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Research relating to McArdle disease by A Lucia and M Pérez is supported by the Health Research Fund of the Spanish Ministry of Health (FIS, ref. #PI061183). Research for the Spanish consortium for the study of McArdle disease is supported by the Health Research Fund (FIS, ref. #PI040487, PI041157, PI040362) and the Spanish Centre for Biomedical Network Research on Rare Diseases (CIBERER). Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Correspondence to Alejandro Lucia.

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Lucia, A., Nogales-Gadea, G., Pérez, M. et al. McArdle disease: what do neurologists need to know?. Nat Rev Neurol 4, 568–577 (2008).

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