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

Bahattin Erdoğan; Gonca Kılıç Yıldırım; Ezgi Susam; Aziz Serhat Baykara

doi:10.1515/jpem-2024-0622

Article

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

Bahattin Erdoğan , Gonca Kılıç Yıldırım , Ezgi Susam and Aziz Serhat Baykara

Published/Copyright: September 9, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 11

Abstract

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

A retrospective analysis was conducted on 350 muscle biopsies performed between 2013 and 2024 in a tertiary care center.

Results

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.

Keywords: metabolic myopathy; glycogen storage diseases; McArdle disease; myophosphorylase; GSD type V

Corresponding author: Bahattin Erdoğan, Department of Pathology, Eskisehir City Hospital, 26080, Eskisehir, Türkiye, E-mail: bhttnrdgn@gmail.com

Research ethics: Scientific Research Ethics Committee (Decision Date: 14/03/2024, Decision No: ESH/BAEK 2024/4).
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Bahattin Erdoğan, conception, design, funding, materials, data collection, processing and writing. Gonca K. Yıldırım, design, supervisor, analysis, critical review. Ezgi Susam, analysis and critical review. Serhat Baykara, literature review, critical analysis.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable – no new data generated.
Information on where and when the study was previously presented: Our study was presented as an oral presentation at the VII. Neuromuscular Diseases Congress (2024).

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Received: 2024-12-28

Accepted: 2025-08-25

Published Online: 2025-09-09

Published in Print: 2025-11-25

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Articles in the same Issue

https://doi.org/10.1515/jpem-2024-0622

Keywords for this article

metabolic myopathy; glycogen storage diseases; McArdle disease; myophosphorylase; GSD type V