568 NATURE CLINICAL PRACTICE NEUROLOGY OCTOBER 2008 VOL 4 NO 10 www.nature.com/clinicalpractice/neuro McArdle disease: what do neurologists need to know? Alejandro Lucia*, Gisela Nogales-Gadea, Margarita Pérez, Miguel A Martín, Antoni L Andreu and Joaquín Arenas Continuing Medical Education online Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. Medscape, LLC designates this educational activity for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To receive credit, please go to http://www.medscape.com/cme/ncp and complete the post-test. Learning objectives Upon completion of this activity, participants should be able to: 1 Describe the organs affected by McArdle’s disease. 2 Describe the primary inheritance pattern of McArdle’s disease. 3 Describe the clinical features associated with McArdle’s disease. 4 List the manifestations of acute crises associated with McArdle’s disease. 5 List the current treatment modalities for McArdle’s disease. Competing interests The authors, the Journal Editor H Wood and the CME questions author D Lie declared no competing interests. INTRODUCTION Glycogenosis type V, also known as glycogen storage disease type V (GSD-V) or myophosphorylase defi- ciency (Online Mendelian Inheritance in Man® [OMIM®; Johns Hopkins University, Baltimore, MD, USA] number 232600), is the most common disorder of skeletal muscle carbohydrate metabo- lism and one of most frequent genetic myopathies (estimated prevalence ~1:100,000 in the Dallas Forth Worth area, TX, USA). 1 This disorder is usually known as ‘McArdle disease’, in homage to the British physician Brian McArdle who first described it in 1951. 2 Patients with McArdle disease have mutations in both alleles of the PYGM gene, which encodes myophosphorylase, the skeletal muscle isoform of glycogen phosphorylase. These mutations result in a lack of functional mature protein. 3 As the liver and heart isoforms of glycogen phosphorylase are unaffected, McArdle disease presents as a pure SUMMARY 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. KEYWORDS exercise intolerance, glycogen storage disease, glycogenosis, myopathy, myophosphorylase A Lucia is a Professor of Exercise Physiology and M Pérez is an Associate Professor of Exercise Physiology at the European University of Madrid, Madrid, Spain. G Nogales-Gadea, MA Martín, AL Andreu and J Arenas are affiliated with the Centre for Biomedical Network Research on Rare Diseases in Barcelona and Madrid, Spain. Correspondence *Department of Physiology, Universidad Europea de Madrid, E-28670 Villaviciosa de Odón, Madrid, Spain alejandro.lucia@uem.es Received 26 June 2008 Accepted 7 August 2008 www.nature.com/clinicalpractice doi:10.1038/ncpneuro0913 REVIEW CRITERIA Pubmed was searched using Entrez for articles published up to mid-June 2008. Search terms included “McArdle(’s)”, “glycogenosis” and “myophosphorylase”. Owing to limitations on the number of references, we cited only those articles that we judged most important and applicable for clinical practice. CME REVIEW