Muscle biopsy specimens from 48 patients with biochemically proven phosphorylase deficiency (McArdle’s disease) have been analyzed by gel electrophoreis (SCS-PAGE), immunoblotting, and immunotitration (ELISA) at Columbia University College of Physicians and Surgeons, New York, NY. The majority had no detectable enzyme protein, 6 had markedly decreased phosphorylase protein, and only 1 had a normal amount of protein. The presence or absence of enzyme protein was not correlated with the clinical presentation or muscle glycogen concentration. In 4 patients tested, messenger RNA was normal in 2, abnormally short in 1, and absent in 1, suggesting heterogeneity of the molecular lesion in McArdle’s disease. 
COMMENT. McArdle’s disease (muscle phosphorylase deficiency; glycogenosis type V) is manifested by exercise intolerance with myalgia, early fatigue, and muscle stiffness relieved by rest. Strenuous exercise is accompanied by acute muscle necrosis and myoglobinuria. Patients presenting in infancy or childhood may have a mild congenital muscle weakness, tiredness or poor stamina without cramps or myoglobinuria, or severe, rapidly progressive weakness soon after birth that results in respiratory failure and death in infancy. The various types of myophosphorylase protein and messenger RNA observed in the above patient population were consistent with at least 5 different mutations that give rise to McArdle’s disease.