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.

Cases — McArdle’s Disease (Type V Glycogen Storage Disease)

• Case 1 — Exercise Intolerance in Teenager 🏃: A 16-year-old boy reports severe muscle cramps and fatigue within minutes of starting football training. He describes “second wind” phenomenon (able to continue after brief rest). Urine occasionally dark after exertion. Diagnosis: McArdle’s disease (myophosphorylase deficiency). Management: Avoid intense anaerobic activity; gentle aerobic exercise; carbohydrate intake before activity; hydration to reduce risk of rhabdomyolysis.
• Case 2 — Rhabdomyolysis with Myoglobinuria 🩸: A 25-year-old woman collapses after sprinting at the gym. She develops severe muscle pain and passes dark brown urine. Labs: CK >20,000 U/L, creatinine elevated. Diagnosis: McArdle’s disease presenting with exertional rhabdomyolysis. Management: IV fluids to prevent acute kidney injury; long-term exercise counselling and dietary adjustments.
• Case 3 — Adult with Chronic Fatigue and Weakness ⏳: A 35-year-old man reports years of exercise intolerance and early fatigue, wrongly labelled as “unfit.” Exam: mild proximal weakness post-exertion; no fixed weakness. Muscle biopsy: absence of myophosphorylase. Diagnosis: McArdle’s disease with chronic exercise intolerance. Management: Education, exercise pacing, creatine and vitamin B6 trials in some patients; genetic counselling.

Teaching Commentary 🧠

McArdle’s disease = autosomal recessive myophosphorylase deficiency (muscle glycogen can’t be broken down). Key clues: - Early fatigue, cramps, pain on exertion. - Second-wind phenomenon (symptoms improve after 10 min due to switch to lipid metabolism). - Rhabdomyolysis → myoglobinuria → risk of AKI. - CK elevated, muscle biopsy shows absent myophosphorylase; genetic testing confirms. Management is lifestyle-based: avoid intense anaerobic exercise, pre-exercise sucrose intake, gentle aerobic activity, hydration, supportive care. Prognosis: normal lifespan but reduced exercise capacity.