A disease that is difficult to predict: regional distribution and phenotypic, histopathological and genetic findings in McArdle disease.

Objectives: McArdle disease (also known as glycogen storage disease type V) is a rare metabolic myopathy that is caused by myophosphorylase deficiency, leading to impaired glycogenolysis in skeletal muscles. This study explored the clinical, histopathological, and genetic landscape of McArdle disease in a regional cohort from Turkey, emphasizing diagnostic and management challenges.

Methods and results: A retrospective analysis was conducted on 350 muscle biopsies performed between 2013 and 2024 in a tertiary care center. Seven patients (2.1 %) were diagnosed with McArdle disease. The clinical features included exercise intolerance (100 %), muscle pain (75 %), and the second wind phenomenon (62.5 %). Two patients presented with acute renal failure due to rhabdomyolysis with myoglobinuria, leading to metabolic acidosis. Histopathological findings revealed glycogen accumulation in subsarcolemmal vacuoles and absent myophosphorylase activity in all cases. Genetic analysis identified five distinct PYGM pathogenic variants, including c.808C>T (p.Arg270Ter) and c.2262del (p.Lys754fs). These findings highlight the phenotypic and genetic heterogeneity of McArdle disease.

Conclusions: McArdle disease remains underdiagnosed due to its variable clinical presentation and limited access to advanced diagnostic tools. This study underscores the importance of a multidisciplinary approach that integrates clinical assessment, muscle biopsy, and molecular analysis. Increased awareness and training among healthcare providers are critical for early recognition and intervention. Future research should focus on expanding genetic databases and exploring targeted therapies to improve outcomes in this challenging condition.