Makindo Medical Notes

Related Subjects: |Autosomal Dominant |Autosomal Recessive |X Linked Recessive

Increased glycogen in muscle which the muscle cannot break down

About

• McArdle Disease: Also known as Glycogen Storage Disease Type V (GSDV).
• It is an autosomal recessive disorder, affecting the metabolism of glycogen in skeletal muscles.
• The disease typically presents in otherwise healthy adults, adolescents, or children who experience exercise intolerance.
• Glycogen is the primary source of energy for high-intensity muscle activity, and the inability to break down glycogen leads to symptoms during exertion.

Aetiology

• Deficiency of myophosphorylase: The disease is caused by a deficiency of the enzyme myophosphorylase (also called muscle phosphorylase), which is essential for breaking down glycogen into glucose-1-phosphate in muscle cells.
• This deficiency prevents the conversion of glycogen to glucose-6-phosphate, impairing energy production during intense physical activity.

Clinical Features

• Exercise intolerance: Patients experience early fatigue, muscle pain (myalgia), and cramps during high-intensity physical activity.
• Second wind phenomenon: After a period of rest, patients often describe a "second wind," where muscle performance improves as the body switches to fatty acid metabolism for energy.
• Myoglobinuria: Following strenuous exercise, muscle breakdown leads to myoglobin release, causing red or dark-colored urine (myoglobinuria).
• Poor endurance: Patients typically have poor exercise endurance and may experience muscle swelling and fixed muscle weakness after exertion.

Investigations

• Urine analysis: Urine may test positive for myoglobin after strenuous activity, indicating muscle breakdown (rhabdomyolysis).
• Muscle biopsy: A definitive diagnostic tool showing subsarcolemmal deposits of glycogen at the periphery of muscle fibers.
• Serum Creatine Kinase (CK): At rest, CK levels are usually elevated and increase further after exercise.
• Genetic testing: DNA analysis of peripheral white blood cells can confirm mutations in the gene that encodes myophosphorylase (PYGM gene).

Management

• Oral sucrose: Taking oral sucrose (approximately 30 grams) before exercise can provide an alternative energy source, improving tolerance to physical activity.
• Aerobic exercise: Moderate-intensity aerobic exercises (e.g., walking or swimming) are recommended, as these activities primarily use fat for energy and are better tolerated.
• Creatine and Vitamin B6 supplementation: These supplements may help improve energy metabolism and muscle function in some patients.
• Avoidance of anaerobic exercise: High-intensity activities (e.g., sprinting, weightlifting) should be avoided as they can lead to muscle damage and rhabdomyolysis.
• Prognosis: With appropriate management, patients typically have a normal life expectancy and good quality of life.