McArdle disease (GSD V) is a rare skeletal myopathy secondary to a disorder of carbohydrate metabolism. It is an autosomal recessive condition with an incidence of approximately 1 in 100,000 and is caused by the absence of muscle glycogen phosphorylase (myophosphorylase). Clinical features include exercise intolerance which consists of acute crisis of early fatigue and muscle stiffness and contractures, especially at the start of the exercise, that usually disappear if exercise is stopped or the intensity is reduced. These episodes are sometimes accompanied by rhabdomyolysis and myoglobinuria (dark urine).
GSD V was described in 1951 by Brian McArdle. GSD V is caused by pathogenic mutations in the Pygm gene (chromosome 11q13) which encodes the muscle glycogen phosphorylase enzyme (GP-M) (myophosphorylase). It is an autosomic recessive disorder with an estimated prevalence of 1/100,000 with both sexes similarly affected. GP-M catalyses and regulates the breakdown of glycogen into glucose-1-phosphate in muscle fibres . Almost all patients have no detectable myophosphorylase activity, thus they are unable to obtain energy from their muscle glycogen stores and, as a result, commonly experience exercise intolerance . A positive family history can be ident¬ified in 50% of patients , and the most common mutation in the Pygm gene in Caucasians is the p.R50X . The majority of patients (50%) are identified between the ages of 10-30 years with less than 4% of cases diagnosed before 10 years. The true incidence of the disease is unknown due to the benign character of the disease and the resulting missed or late diagnosis.
The diagnosis is based on clinical findings, and supportive laboratory findings of a low or absent myophosphorylase activity on histochemical or biochemical examination of a muscle biopsy and subsequent genetic testing. The absence of increased lactate during exercise and a raised creatine kinase are also features .
Although no specific treatment for the enzyme deficiency is available, affected individuals benefit from a number of therapeutic options which have been shown to reduce symptoms or to enhance the ability for physical activity, moderate aerobic training 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 . There are a number of case reports suggesting a benefit with beta-2-sympathomimetics, vitamin B6 and coenzyme Q10 [7-8]. However, Phoenix et al. reported no significant beneficial effects with Vitamin B6 . The best inter¬vention to do for McArdle patients is appropriate exercise habits. For example, after gradual, supervised training, a 38-year-old patient (with no myophosphorylase activity) could run regularly and cover 10 km in 60 min with no rhabdomyolysis. The average time for recre¬ational runners to complete a 10 km race generally falls between 75–80 min.
The prognosis is good. 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 . There are a small number of case reports of generalised weakness after birth with death occurring in childhood . There are no reports of limitations of life due to cardio-circulatory disease. About 50% of affected individuals have recurrent episodes of myoglobinuria, and 27% of patients have acute renal failure after strenuous exercise . Patients do need to learn how to cope with the disease and how to avoid major muscle damage, which can result in acute rhabdomyolysis and renal failure.