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 and 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. Onset of GSDV typically occurs in the second to third decade of life; however, a severe, rapidly progressive form manifests shortly after birth. Non-progressive weakness occurs in approximately one third of affected individuals, is more likely to involve proximal muscles, and is more common in individuals of advanced age. In some individuals, progressive weakness manifests in the sixth or seventh decade of life. Approximately 50% of individuals have episodes of myoglobinuria that can result in acute renal failure.
GSDV is diagnosed by clinical findings, supportive laboratory findings (i.e., increased resting serum creatine kinase [CK] concentration 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 either by assay of myophosphorylase enzyme activity or by molecular genetic testing of PYGM (encoding glycogen phosphorylase, muscle form), the only gene associated with GSDV. Targeted mutation analysis of the most common mutations, p.Arg50X and p.Gly205Ser, and sequence analysis of the entire coding region are available on a clinical basis.
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 his/her being a carrier is 2/3. Heterozygotes are generally asymptomatic. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the mutations have been identified in the family.