Which enzyme deficiency characterizes Pompe disease (Glycogen Storage Disease Type II)?

Explanation

## Pompe Disease (GSD Type II) **Key Point:** Pompe disease is caused by deficiency of **acid α-glucosidase** (also called lysosomal acid maltase), a lysosomal enzyme responsible for degrading glycogen within lysosomes. ### Enzyme Function Acid α-glucosidase catalyzes the hydrolysis of α-1,4 and α-1,6 glycosidic bonds in the lysosomal compartment. Without this enzyme, glycogen accumulates massively in lysosomes, particularly in cardiac and skeletal muscle. ### Clinical Presentation - **Infantile form (classic):** Presents before age 2 with severe cardiomegaly, hypotonia, developmental delay, and early death (usually by age 2–3 years) - **Late-onset form:** Presents in childhood or adulthood with progressive skeletal muscle weakness and respiratory compromise; cardiac involvement is minimal ### Pathophysiology Unlike other GSDs where glycogen accumulates in the cytoplasm, Pompe disease features **lysosomal glycogen accumulation**, leading to lysosomal rupture and myocyte death. **High-Yield:** Pompe disease is the ONLY glycogen storage disorder with a lysosomal enzyme defect — all others involve cytoplasmic or mitochondrial enzymes. ### Treatment - Enzyme replacement therapy (ERT) with imiglucerase or avalglucosidase is now standard of care - ERT dramatically improves survival and reduces cardiomegaly in infantile-onset disease [cite:Robbins 10e Ch 7]