The Impact of Muscle Fatigue on McArdle Disease: A Case Report

McArdle disease (McA) is a rare metabolic disorder of autosomal recessive inheritance caused by pathogenic variants in the PYGM gene, which lead to a deficiency of the myophosphorylase enzyme. This enzymatic defect impairs muscle glycogenolysis, typically resulting in exercise intolerance, premature fatigue, and exertional cramps triggered by anaerobic or high-intensity physical activity starting in childhood or adolescence. However, the diagnosis is frequently delayed due to the heterogeneous and non-specific presentation of these symptoms. The authors report a case of a 61-year-old woman with a lifelong history of exercise intolerance and disproportionate muscle fatigue that restricted her physical activity since her youth. She presented with persistent, idiopathic elevations of creatine kinase (CK) over several years. The patient had no history of myoglobinuria and showed preserved renal function and no evidence of acute rhabdomyolysis, despite marked hyperCKemia. Cardiac involvement was also excluded. After excluding more common secondary causes of hyperCKemia, such as statin-induced myopathy and inflammatory conditions, the persistence of marked hyperCKemia and specific exercise-induced symptoms suggested a metabolic myopathy, such as McArdle disease. Molecular analysis was performed, identifying the homozygous pathogenic variant c.280C>T (p.Arg94Trp) in the PYGM gene and confirming the diagnosis of McArdle disease.