A 5-month-old infant presents with severe hypotonia, macroglossia, and progressive cardiomegaly with heart failure. Echocardiography shows massive biventricular hypertrophy. Muscle biopsy reveals vacuoles filled with PAS-positive material, and serum creatine kinase is elevated. Blood glucose is normal and there is no hepatomegaly. Deficiency of which enzyme best explains these findings?

• A Debranching enzyme (alpha-1,4 to alpha-1,6 transferase)
• B Muscle glycogen phosphorylase in cytosol
• C Acid alpha-glucosidase (acid maltase) in lysosomes ✓
• D Branching enzyme (amylo-1,4 to 1,6 transglucosidase)

Explanation

This is Pompe disease (GSD type II), caused by deficiency of lysosomal acid alpha-glucosidase. Glycogen accumulates inside lysosomes, producing cardiomyopathy, hypotonia, and macroglossia with normal blood glucose because cytosolic glycogenolysis remains intact. McArdle disease (option B) affects skeletal muscle only, with exercise intolerance rather than cardiac failure, and debranching enzyme deficiency (Cori disease, option A) features prominent hepatomegaly.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.