McArdle disease is caused by deficiency of which enzyme?

• A. Muscle phosphorylase
• B. Hepatic glycogen phosphorylase
• C. Debranching enzyme
• D. Lysosomal alpha-glucosidase

Answer: (A)

McArdle disease arises from a deficiency of muscle glycogen phosphorylase, also called myophosphorylase. This enzyme is needed to break down glycogen stored in skeletal muscle during exercise. When it’s missing, muscles can’t access their glycogen for quick energy, so exercise tolerance is reduced, with cramps and sometimes myoglobinuria after strenuous activity. Because glycogenolysis in muscle is impaired, the usual rise in lactate during intense effort is blunted, while other energy pathways can still function, which explains the characteristic metabolic and clinical picture.

Other enzyme defects affect different tissues or steps: hepatic glycogen phosphorylase deficiency causes liver-specific disease with hepatomegaly and fasting hypoglycemia; a debranching enzyme defect (Cori disease) disrupts normal glycogen structure and presents with fasting hypoglycemia and hepatomegaly; lysosomal alpha-glucosidase deficiency (Pompe disease) leads to lysosomal glycogen accumulation, impacting heart and skeletal muscle, particularly in infants.