ENOrphanet Journal of Rare Diseases | Exercise Intervention in Children and Young Adults with McArdle Disease: Feasibility, Acceptability, and Clinical Outcomes
Date: March 01, 2026
Classification: Frontiers
Recommend:
This study is the first to evaluate the feasibility and safety of remotely supervised exercise interventions in children and young adults with McArdle disease, providing important clinical practice references for this rare metabolic myopathy population.
Literature Overview
The article titled 'An exercise intervention in children and young adults with McArdle disease: feasibility, acceptability, and clinical outcomes,' published in Orphanet Journal of Rare Diseases, reviews and summarizes a 12-week remotely supervised exercise intervention study in McArdle disease patients aged 5–30 years. Using multidimensional assessments (including cardiopulmonary exercise testing, muscle strength, near-infrared spectroscopy, quality of life, etc.), the study explored the feasibility, safety, and acceptability of the intervention and conducted a preliminary analysis of its impact on clinical outcomes. Results showed that although no statistically significant improvements were observed, trends suggest potential individual clinical benefits. This study lays the foundation for future large-scale exercise intervention trials in younger McArdle populations.Background Knowledge
McArdle disease (Glycogen Storage Disease type V, GSD V) is an autosomal recessive metabolic myopathy caused by a deficiency in muscle phosphorylase (encoded by the PYGM gene), which blocks the breakdown of glycogen into glucose-1-phosphate, thereby impairing anaerobic glycolysis for energy production. Patients commonly experience muscle pain, cramps, weakness, and easy fatigability during exercise, with severe cases potentially leading to rhabdomyolysis, myoglobinuria, and renal injury. The characteristic 'second wind' phenomenon manifests as worsening symptoms at the onset of exercise, which typically resolve after about 7 minutes when the body switches to fat and blood glucose oxidation for energy. Due to impaired glycogenolysis, patients generally exhibit reduced aerobic capacity, with VO2peak typically reaching only ~50% of predicted normal values. Current clinical guidelines for adult McArdle disease recommend regular aerobic and resistance training to improve fitness and quality of life, but evidence supporting such interventions in children and adolescents is lacking. Additionally, safely and effectively assessing exercise tolerance in this population (e.g., using CPET) remains challenging, as high-intensity testing may trigger rhabdomyolysis. Therefore, exploring structured, remotely supervised exercise intervention programs suitable for younger patients and evaluating their feasibility and safety holds significant clinical translational value. This study fills a critical gap in the field, providing preliminary data to inform age-specific exercise prescriptions.
Methods and Experiment
The study recruited genetically confirmed McArdle disease patients aged 5–30 years from metabolic clinics in New South Wales, Australia, for a 12-week remotely supervised exercise intervention. Primary outcomes included feasibility (enrollment rate, adherence), safety, and acceptability. Each participant completed two assessment visits (baseline and post-intervention), including cardiopulmonary exercise testing (CPET using a treadmill STEEP protocol), muscle strength tests (leg press, lat pulldown, etc.), near-infrared spectroscopy (NIRS) for muscle oxygenation monitoring, quality of life questionnaires (PROMIS), habitual physical activity monitoring (Actigraph), and hematological tests (CK, ALT, AST). The exercise intervention consisted of three 60-minute remote supervised sessions per week, including walking warm-up until the 'second wind' was reached, followed by circuit training (resistance + aerobic). Exercise intensity was controlled by target heart rate (50–75% of predicted maximum), RPE (5–7), and pain score (0–1). Adherence, adverse events, technical issues, and participant feedback were all recorded.Key Conclusions and Findings
Implications and Future Directions
This is the first exploratory study to systematically evaluate exercise interventions in children and young adults with McArdle disease, confirming the feasibility, safety, and high acceptability of remote supervision models, providing key parameters for the design of future multicenter, large-sample randomized controlled trials (e.g., expected adherence, safety monitoring focus).
Although no significant group-level improvements were observed, individual trends suggest some patients may benefit, underscoring the importance of individualized responses. The study also reveals limitations of current assessment tools—treadmill CPET may not fully activate the 'second wind' due to increasing incline, suggesting future studies consider using cycle ergometry or submaximal testing to reduce risk and improve sensitivity. Additionally, NIRS, as a non-invasive monitoring tool, shows promise and warrants further exploration for guiding exercise prescription.
Conclusion
This study systematically evaluated the implementation of a 12-week remotely supervised exercise intervention in children and young adults with McArdle disease. The results demonstrate that the intervention has good feasibility and acceptability under real-world conditions, with no severe adverse events, confirming its safety. Although no significant improvements in aerobic capacity, muscle strength, or quality of life were observed at the group level, data analysis suggests trends toward individual clinical benefits, such as reduced exercise-induced pain, improved muscle strength, and enhanced muscle oxygen utilization. These findings highlight the potential value of structured exercise training in this young rare disease population. The study also reveals limitations of current assessment methods—treadmill CPET may affect result accuracy due to terrain changes—suggesting future adoption of more suitable testing modalities. Overall, this study establishes a methodological foundation for subsequent large-scale, long-term follow-up clinical trials, supporting the integration of individualized, remotely supervised exercise programs as part of comprehensive McArdle disease management to improve patients’ long-term function and quality of life.
