Gene Summary
RefSeq / NCBIThis gene encodes a muscle enzyme involved in glycogenolysis. Highly similar enzymes encoded by different genes are found in liver and brain. Mutations in this gene are associated with McArdle disease (myophosphorylase deficiency), a glycogen storage disease of muscle. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]
Clinical Phenotype
McArdle disease (GSD type V): exercise intolerance with myalgia, cramps, and myoglobinuria triggered by brief intense or sustained moderate exercise. Characteristic 'second wind' phenomenon. CK elevated at baseline; markedly elevated after exertion.
Molecular Mechanism
Muscle glycogen phosphorylase initiates glycogenolysis in skeletal muscle. Its absence blocks the initial high-power glycolytic phase of exercise. After ~10 minutes of low-intensity exercise, fatty acid oxidation and glucose delivery take over — producing the second wind.
Clinical Hallmarks & Key Evidence
The 'second wind' phenomenon — relief of cramps and renewed exercise capacity after resting briefly during sustained effort — is pathognomonic for McArdle disease.
McArdle B. Clin Sci. 1951;10(1):13-35.
Non-ischemic forearm exercise test: lactate fails to rise normally (stays flat) while ammonia rises appropriately — confirming a glycogenolytic defect without the risk of venous occlusion.
Kazemi-Esfarjani P et al. Ann Neurol. 2002;52(2):153-59.
The p.R49X variant (also called p.R50X in older nomenclature) accounts for ~81% of McArdle alleles in White Europeans — making targeted genotyping highly efficient in this population.
Andreu AL et al. Am J Hum Genet. 1999;65(1):229-32.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.