A 6-year-old boy from rural Maharashtra presents with recurrent episodes of muscle pain and dark urine after exercise. Serum creatine kinase is markedly elevated (8000 U/L). Genetic testing confirms muscle phosphorylase deficiency. Regarding this condition and related glycogen storage disorders, all of the following are true EXCEPT:

Explanation

## Clinical Case: McArdle Disease (GSD Type V) ### Key Point: **The PYGL gene encodes liver phosphorylase, NOT muscle phosphorylase.** This patient has muscle phosphorylase deficiency, which is caused by mutations in the **PYGM gene** (muscle isoform), not PYGL. This is a critical distinction in GSD Type V genetics. ### Pathophysiology of McArdle Disease ```mermaid flowchart TD A[Muscle phosphorylase deficiency]:::outcome --> B[Glycogen cannot be mobilized to glucose-1-phosphate]:::outcome B --> C{Energy demand during exercise}:::decision C -->|Early phase| D[ATP depletion, anaerobic metabolism]:::urgent D --> E[Rhabdomyolysis, myoglobinuria]:::urgent C -->|Continued exercise| F[Blood glucose uptake increases]:::action F --> G["Second wind" phenomenon]:::outcome H[PYGM gene mutation]:::outcome --> A ``` ### High-Yield: Phosphorylase Isoforms | Isoform | Gene | Tissue | GSD Type | Clinical Feature | |---------|------|--------|----------|------------------| | **Muscle (PYGM)** | PYGM | Skeletal & cardiac muscle | **Type V (McArdle)** | Exercise intolerance, myoglobinuria, second wind | | **Liver (PYGL)** | PYGL | Liver | **Type VI** | Mild hepatomegaly, generally benign | | **Brain** | PYGB | Brain, RBCs | — | Rare deficiency | ### Clinical Pearl: **Oral glucose/fructose loading** works in McArdle disease because: 1. Glucose is transported into muscle via GLUT4 (insulin-independent during exercise) 2. Glucose-6-phosphate enters glycolysis directly, bypassing the phosphorylase block 3. This provides ATP and reduces reliance on anaerobic metabolism 4. Symptoms improve markedly ### Correct Statements Verified **Statement 1 (Myoglobinuria mechanism):** ✓ Correct. Muscle phosphorylase deficiency prevents glycogenolysis → ATP depletion → anaerobic metabolism → lactate accumulation → rhabdomyolysis → myoglobinuria. **Statement 2 (Glucose/fructose benefit):** ✓ Correct. Pre-exercise carbohydrate loading is a standard management strategy for McArdle disease patients. **Statement 4 (Muscle biopsy findings):** ✓ Correct. Subsarcolemmal (vacuolar) glycogen accumulation is characteristic. The glycogen structure is *normal* (normal branching pattern) but the *quantity* is excessive because it cannot be mobilized. ### Mnemonic: **"PYGM = Muscle, PYGL = Liver"** — Remember the letter M in PYGM for Muscle phosphorylase.