Which clinical feature best distinguishes Pompe disease (GSD II) from other glycogen storage disorders?

Explanation

## Distinguishing Feature of Pompe Disease ### Pathophysiology **Key Point:** Pompe disease (GSD II) is caused by deficiency of acid α-glucosidase (lysosomal enzyme), leading to glycogen accumulation specifically within lysosomes rather than cytoplasm. ### Clinical Presentation Comparison | Feature | Pompe (GSD II) | Other GSDs (I, III, V, VII) | |---------|---|---| | **Organ involvement** | Heart + skeletal muscle | Liver + muscle OR muscle alone | | **Cardiomegaly** | Prominent, life-threatening | Absent | | **Muscle weakness** | Early, progressive (infantile form) | Variable; often spares heart | | **Hepatomegaly** | Mild or absent | Marked | | **Hypoglycemia** | Absent | Present (especially GSD I, III) | | **Enzyme defect** | Lysosomal acid α-glucosidase | Cytoplasmic/mitochondrial enzymes | | **Glycogen location** | Lysosomes | Cytoplasm | ### High-Yield Distinction **High-Yield:** The **cardiac involvement** (cardiomegaly with heart failure) is the pathognomonic discriminator of Pompe disease. No other GSD presents with prominent cardiomegaly as a primary feature. **Clinical Pearl:** Infantile-onset Pompe disease (< 2 years) presents with "floppy baby" syndrome, hypotonia, and massive cardiomegaly; death typically occurs by age 2 without enzyme replacement therapy (ERT). Adult-onset Pompe is milder, with late-onset muscle weakness. **Mnemonic:** **POMPE = Pump failure** — remember the cardiac involvement as the key distinguishing feature. ### Why Cardiomegaly Occurs Lysosomes in cardiac myocytes accumulate glycogen → cellular dysfunction → hypertrophy and dilated cardiomyopathy → congestive heart failure. [cite:Robbins 10e Ch 7]