Abstract
McArdle disease, or glycogen storage disease type V, is a rare inherited metabolic myopathy caused by mutations in the PYGM gene, resulting in deficiency of the enzyme myophosphorylase. Patients usually present with lifelong exercise-induced fatigue, muscle pain, and sometimes rhabdomyolysis, but the condition is underdiagnosed due to its nonspecific manifestations. This case is distinctive because it documents molecularly confirmed McArdle disease in a woman with persistently elevated creatine kinase and a suggestive family history, underlining the importance of clinical suspicion, timely genetic testing, and appropriate counselling. A 35-year-old woman reported lifelong myalgia and easy fatigability. Her past history included recurrent migraines and use of a progestogen-only contraceptive. One sister, aged 21, had similar symptoms, while her other sister and parents were healthy. Physical examination was unremarkable. Laboratory tests showed an isolated elevation of creatine kinase (1,504 U/l). Genetic analysis revealed the PYGM c.148C>T, p.(Arg50*) variant in apparent homozygosity, a rare mutation transmitted in heterozygosity. At follow-up she was 30 weeks pregnant and was referred, along with her symptomatic sister, to a genetic consultation. Behavioural guidance focused on regular moderate exercise and symptom management. McArdle disease is underdiagnosed because its symptoms are often misinterpreted as poor physical fitness. This case highlights that early recognition, and molecular confirmation can avoid unnecessary invasive tests and provide clarity in patients with chronic exertional intolerance. The identification of a rare PYGM variant further emphasizes the importance of genetic counselling, which enables family screening and informed reproductive planning. Timely recognition and tailored management are essential for improving patient quality of life. LEARNING POINTS: Early recognition and diagnosis McArdle's disease is underdiagnosed due to nonspecific symptoms. This case highlights the importance of maintaining clinical suspicion for timely diagnosis.Impact on quality of life Although no curative treatment exists, simple measures such as regular moderate exercise and carbohydrate intake can substantially improve symptoms and daily functioning.Value of genetic counselling Genetic confirmation allows family screening, clarifies prognosis, and supports individualized management strategies for patients and their relatives.