Myopathic Symptoms and Exercise Tolerance in Adolescent Patients With Long-Chain Fatty Acid Oxidation Disorders

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Long-chain fatty acid oxidation disorders (lcFAOD) are genetic conditions affecting energy metabolism.
• Rhabdomyolysis, or muscle breakdown, is a common symptom, often triggered by physical exertion.
• The long-term impact of lcFAOD on exercise capacity and muscle health in adolescents identified through newborn screening (NBS) is not fully understood.

Purpose of the Study:

• To evaluate the physiological responses to exercise, muscle symptoms, and physical activity levels in adolescent patients with lcFAOD.
• To determine the extent to which NBS cohorts develop the myopathic phenotype associated with lcFAOD.
• To identify factors that may increase the risk of rhabdomyolysis during or after exercise in this population.

Main Methods:

• Cardiopulmonary exercise testing (incremental and prolonged) was conducted on 14 adolescent lcFAOD patients.
• A symptom-based questionnaire assessed muscle pain and rhabdomyolysis triggers.
• The Short Questionnaire to Assess Health-enhancing physical activity was used to measure activity levels.

Main Results:

• Patients exhibited a decreased ventilatory anaerobic threshold, relative peak oxygen uptake, and relative peak work rate compared to controls.
• No adverse events occurred during prolonged exercise under well-fed conditions.
• Provoking factors like infection or inadequate intake significantly increased the risk of rhabdomyolysis.
• Despite normal weekly physical activity levels, 46% of screened and 100% of symptomatic patients reported debilitating muscle pain.

Conclusions:

• Adolescent lcFAOD patients demonstrate impaired exercise physiology and experience significant muscle symptoms, even with regular physical activity.
• Rhabdomyolysis risk is elevated when other stressors are present, emphasizing the importance of managing these factors.
• Exercise testing can be a valuable tool for monitoring and guiding exercise recommendations in lcFAOD patients identified through NBS.