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Glycogen Storage Disease Type V.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
2006 Apr 19 [updated 2014 Jun 26].



Glycogen storage disease type V (GSDV, McArdle disease) is a metabolic myopathy characterized by exercise intolerance manifested by rapid fatigue, myalgia, and cramps in exercising muscles. Symptoms usually are precipitated by isometric exercise or sustained aerobic exercise. Most individuals improve their exercise tolerance by exploiting the "second wind" phenomenon with relief of myalgia and fatigue after a few minutes of rest. Age of onset is frequently in the first decade of life but can vary. Fixed muscle weakness occurs in approximately 25% of affected individuals, is more likely to involve proximal muscles, and is more common in individuals of advanced age. Approximately 50% of affected individuals have recurrent episodes of myoglobinuria that could eventually result in acute renal failure, although reported cases are rare.


GSDV is diagnosed by clinical findings, supportive laboratory findings (i.e., increased resting serum creatine kinase [CK] activity and no change in plasma lactate concentration on the forearm non-ischemic or ischemic test), and the cycle test (a specific, sensitive, and simple test that is based on the pathognomonic heart rate response observed in the second wind phenomenon). The diagnosis is confirmed by molecular genetic testing of PYGM (encoding glycogen phosphorylase, muscle form), the only gene known to be associated with GSDV. Targeted mutation analysis identifies the most common pathogenic variants, p.Arg50Ter and p.Gly205Ser. Assay of myophosphorylase enzyme activity confirms the diagnosis when genetic diagnosis is unclear.


Treatment of manifestations: Although no cure for GSDV is available, affected individuals benefit from moderate-intensity aerobic training (e.g., walking or brisk walking, bicycling) to increase cardiorespiratory fitness and muscle oxidative capacity. Pre-exercise ingestion of sports drinks containing simple carbohydrates improves exercise tolerance and may protect against exercise-induced rhabdomyolysis. Prevention of secondary complications: Caution with general anesthesia because it may cause acute muscle damage. Surveillance: Annual routine physical examination and review of diet. Agents/circumstances to avoid: To prevent occurrence of cramps and myoglobinuria, avoid intense isometric exercise and maximal aerobic exercise. Evaluation of relatives at risk: When the family-specific pathogenic variants are known, early detection of GSDV in relatives at risk ensures proper management to prevent muscle injury leading to rhabdomyolysis and to improve long-term outcome – particularly by adoption of a healthy lifestyle (i.e., regular exercise practice such as brisk walking) in childhood.


GSDV is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the risk of being a carrier is 2/3. Heterozygotes are asymptomatic. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants have been identified in the family.

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