Myophosphorylase deficiency (McArdle's disease), or glycogen storage disease type 5 (GSD5) , is a severe form of glycogen storage disease characterized by exercise intolerance. Prevalence is unknown. Onset occurs in childhood. Patients present with a syndrome of muscular exercise intolerance with myalgia, cramps, fatigue, and muscle weakness. Massive elevation of creatine-kinase and rhabdomyolysis with myoglobinuria (dark urine) after exercise is noted in around 50% of patients, potentially leading to acute kidney failure. A 'second wind' phenomenon with relief of myalgia and fatigue after a few minutes of rest is observed in many patients. The clinical presentation is usually very classical, but some patients may have very moderate forms. In a few cases, onset very early in life with hypotonia, generalized muscle weakness and progressive respiratory failure has been described. The condition is caused by mutations in the PYGM gene (11q13), leading to muscle phosphorylase deficiency. Mutation p.R50X may account for 40% to 50% of the alleles in Caucasian populations. The condition is autosomal recessive. The diagnosis is based on biological findings revealing a lack of lactate elevation in blood during ischemic forearm test, excess glycogen, and deficient phosphorylase activity in the muscle biopsy. The differential diagnosis should include GSD type 7 (see this term). Treatment is based on controlled physical training in order to develop mitochondrial oxidation capacities in muscles, and programmed glucose intake according to exercising periods. Diets with high protein intake have yielded variable results. Prognosis is favorable when severe rhabdomyolysis is avoided. However, myoglobinuria may lead to potentially life-threatening renal failure.
Last update: September 2009