A 12-year-old girl from Delhi presents with progressive muscle weakness, myalgia, and dark-colored urine after strenuous exercise. Serum creatine kinase is 8,500 U/L, myoglobin is elevated, and urine myoglobin is positive. Her mother reports a similar episode 2 years ago. Muscle biopsy shows excess glycogen with normal structure. Phosphorylase activity is normal. What is the most appropriate next step in management?

Explanation

## Clinical Diagnosis This presentation is consistent with **Type V Glycogen Storage Disease (GSD V)** — **Muscle Phosphorylase Deficiency** (McArdle Disease). ### Key Diagnostic Features - Exercise-induced myalgia and muscle weakness - Myoglobinuria (dark urine) after exertion - Elevated CK and myoglobin - Normal phosphorylase activity on muscle biopsy is a **red herring** — the question states it is normal, but in GSD V it is **absent or severely reduced**. However, the clinical picture (exercise-induced rhabdomyolysis with glycogen accumulation) is diagnostic. - Recurrent episodes triggered by exertion ## Acute Management: Preventing Acute Kidney Injury (AKI) **Key Point:** Exercise-induced myoglobinuria carries a high risk of acute tubular necrosis (ATN) and acute kidney injury. The immediate priority is to prevent renal failure, not to address the underlying metabolic defect. ### Management Algorithm ```mermaid flowchart TD A[Exercise-induced rhabdomyolysis<br/>with myoglobinuria]:::outcome --> B{Immediate action?}:::decision B -->|Prevent AKI| C[IV hydration<br/>target UOP 200-300 mL/hr]:::action C --> D[Alkalinize urine<br/>sodium bicarbonate to pH > 6.5]:::action D --> E[Monitor creatinine,<br/>potassium, CK]:::action E --> F{Renal function stable?}:::decision F -->|Yes| G[Discharge with<br/>exercise counseling]:::outcome F -->|No| H[Consider dialysis]:::urgent ``` ### Rationale for IV Hydration + Alkalinization | Intervention | Mechanism | Goal | |---|---|---| | **IV hydration** | Increases glomerular filtration and urine flow | Dilutes myoglobin; reduces tubular obstruction | | **Urine alkalinization** (sodium bicarbonate) | Raises urine pH to > 6.5 | Prevents myoglobin precipitation in acidic urine; myoglobin is soluble at pH > 6.5 | | **Avoid diuretics** | Loop diuretics worsen myoglobin precipitation | Risk of ATN increases | **High-Yield:** Myoglobin is filtered freely at the glomerulus but precipitates in acidic urine (pH < 5.6), causing tubular obstruction and ATN. Alkalinization keeps myoglobin soluble and prevents AKI. ## Long-Term Management (After Acute Phase) - **Exercise avoidance:** Strict counseling on avoiding strenuous activity - **Genetic counseling:** Autosomal recessive inheritance (PYGM gene mutations) - **Dietary modifications:** Frequent small meals with glucose/sucrose before exercise ("second wind" phenomenon — anaerobic metabolism switches to aerobic after initial glycogen depletion) - **Monitoring:** Renal function, electrolytes, CK trends **Clinical Pearl:** Patients with GSD V may experience a "second wind" phenomenon — after 10 minutes of exercise, symptoms improve because the body shifts to aerobic metabolism and uses blood glucose and fatty acids instead of muscle glycogen.