Mcardle Disease

McArdle disease (glycogen storage disease type V) is an autosomal recessive deficiency of muscle glycogen phosphorylase (PYGM).

• Prevalence 1 in 100,000.

• Impaired glycogenolysis causes exertional energy failure and contractures, with myoglobinuria.

• Onset in childhood; diagnosis often delayed to adulthood.

• Second wind phenomenon after 6 to 10 minutes of exercise.

• Exercise intolerance, myalgia, muscle stiffness and painful cramps/contractures with isometric or high intensity exercise.

• Second wind phenomenon (improvement after a short rest or slowing).

• Recurrent rhabdomyolysis with dark urine, acute kidney injury.

• Fixed proximal weakness in older adults.

• CK elevated at rest (often over 1,000 U/L), myoglobinuria after exertion.

• Forearm ischaemic exercise test: no rise in venous lactate with exaggerated ammonia (largely replaced by non ischaemic version).

• PYGM genetic testing (R50X common in Europeans) is diagnostic.

• Muscle biopsy: subsarcolemmal glycogen, absent phosphorylase staining (if genetics unrevealing).

• Exclude other glycolytic defects (PFK, PGAM), lipid myopathies, mitochondrial disease.

• Aerobic conditioning (regular moderate exercise) is the cornerstone; warm up slowly and use the second wind.

• Pre exercise sucrose 37 g (30 to 40 g, e.g. sports drink) 5 minutes before exercise improves tolerance; carbohydrate rich diet.

• Avoid heavy isometric exertion and sudden high intensity activity.

• Rhabdomyolysis: IV fluids to urine output over 200 mL/h, monitor CK, potassium and renal function.

• Vitamin B6 50 to 100 mg daily may help; creatine 150 mg/kg/day modest benefit.

• Statins and drugs causing myopathy should be avoided.

• Genetic counselling.