McArdle disease is arguably the paradigm of exercise intolerance in humans. This disorder is caused by inherited deficiency of myophosphorylase, the enzyme isoform that initiates glycogen breakdown in skeletal muscles. Because patients are unable to obtain energy from their muscle glycogen stores, this disease provides an interesting model of study for exercise physiologists, allowing insight to be gained into the understanding of glycogen-dependent muscle functions. Of special interest in the field of muscle physiology and sports medicine are also some specific (if not unique) characteristics of this disorder, such as the so-called ‘second wind’ phenomenon, the frequent exercise-induced rhabdomyolysis and myoglobinuria episodes suffered by patients (with muscle damage also occurring under basal conditions), or the early appearance of fatigue and contractures, among others. In this article we review the main pathophysiological features of this disorder leading to exercise intolerance as well as the currently available therapeutic possibilities. Patients have been traditionally advised by clinicians to refrain from exercise, yet sports medicine and careful exercise prescription are their best allies at present because no effective enzyme replacement therapy is expected to be available in the near future. As of today, although unable to restore myophosphorylase deficiency, the ‘simple’ use of exercise as therapy seems probably more promising and practical for patients than more ‘complex’ medical approaches.
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No sources of funding were used to assist in the preparation of this review. Alfredo Santalla, Gisela Nogales-Gadea, Niels Ørtenblad, Astrid Brull, Noemi de Luna, Tomàs Pinós and Alejandro Lucia have no potential conflicts of interest that are directly relevant to the content of this review. The authors original research in the field is supported by grants from the Spanish Ministry of Economy and Competitiveness [Fondo de Investigaciones Sanitarias (FIS), grants number PI12/00914 and PI13/00855]. Gisela Nogales-Gadea and Noemi de Luna are supported by Sara Borrell contracts of ISCIII CD10/00027 and CD11/00060, respectively. Astrid Brull is supported by an FIS grant of ISCIII FI11/00709.
A. Santalla, G. Nogales-Gadea, T. Pinós, and A. Lucia contributed equally to this article.
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Santalla, A., Nogales-Gadea, G., Ørtenblad, N. et al. McArdle Disease: A Unique Study Model in Sports Medicine. Sports Med 44, 1531–1544 (2014). https://doi.org/10.1007/s40279-014-0223-5
- Sarcoplasmic Reticulum
- Muscle Glycogen
- Glycogen Phosphorylase
- Exercise Intolerance
- Premature Termination Codon