A 6-year-old boy from Tamil Nadu presents with exercise intolerance, muscle cramps, and dark urine after physical activity. Serum creatine kinase is markedly elevated. Which feature best distinguishes McArdle disease (GSD V) from Pompe disease (GSD II)?

Explanation

## McArdle Disease vs. Pompe Disease: Key Discriminator ### Clinical Context The vignette describes **McArdle disease (GSD V)** — muscle phosphorylase deficiency causing exercise intolerance, myoglobinuria (dark urine), and elevated CK. The critical question asks what distinguishes it from Pompe. ### Comparative Table | Feature | McArdle (GSD V) | Pompe (GSD II) | |---------|---|---| | **Enzyme defect** | Muscle phosphorylase | Acid α-glucosidase (lysosomal) | | **Glycogen location** | Cytoplasmic (muscle) | Lysosomal (all tissues) | | **Cardiomegaly** | **Absent** | **Prominent** | | **Cardiac function** | Normal | Severely impaired | | **Hepatomegaly** | Absent | Mild or absent | | **Muscle involvement** | Severe (exercise-induced) | Severe (resting weakness) | | **Myoglobinuria** | Yes (with exercise) | No | | **Hypoglycemia** | Absent | Absent | | **Age of onset** | Childhood (exercise intolerance) | Infancy (cardiac + muscle) | | **Ischemic forearm test** | No lactate rise (pathognomonic) | Normal lactate rise | ### High-Yield Discriminator **High-Yield:** The **absence of cardiomegaly and preserved cardiac function** is the single best clinical feature distinguishing McArdle disease from Pompe disease. **Key Point:** McArdle disease is a **muscle-specific** disorder; the heart is spared because cardiac myocytes can use glucose via glycolysis and oxidative phosphorylation without relying on muscle phosphorylase. Pompe, by contrast, affects all tissues with lysosomes, making the heart a primary target. **Clinical Pearl:** The **"second wind" phenomenon** is pathognomonic for McArdle disease — patients experience initial muscle pain/cramps with exercise, but symptoms improve after 10 minutes as blood glucose and fatty acid oxidation increase to fuel muscles. **Mnemonic:** **McArdle = Muscle-only** (no cardiac involvement); **Pompe = Pump failure** (cardiac + muscle). ### Why Cardiomegaly Occurs in Pompe but Not McArdle - **Pompe:** Lysosomal enzyme deficiency → glycogen accumulates in ALL cell types, including cardiac myocytes → cardiomyopathy. - **McArdle:** Muscle phosphorylase deficiency → glycogen accumulates only in muscle; cardiac myocytes have alternative energy pathways (glucose uptake, fatty acid oxidation) → heart is spared. [cite:Robbins 10e Ch 7; Harrison 21e Ch 416]