A 28-year-old woman with a history of recurrent myoglobinuria and exercise intolerance is found to have a deficiency of phosphofructokinase (PFK), the rate-limiting enzyme of glycolysis. She presents with severe muscle cramps and dark urine after a 2-hour gym session. Her serum creatinine is 1.2 mg/dL and urine myoglobin is positive. What is the most appropriate immediate management step?

Explanation

## Clinical Context Phosphofructokinase (PFK) deficiency (Glycogen Storage Disease Type VII, Tarui disease) is an autosomal recessive disorder causing inability to convert fructose-1,6-bisphosphate in glycolysis. This results in: - Inability to generate ATP during muscle contraction - Accumulation of glucose-6-phosphate → glycogen buildup - Muscle necrosis during exertion → myoglobinuria - Risk of acute kidney injury (AKI) from myoglobin precipitation in renal tubules ## Pathophysiology of Myoglobinuria-Induced AKI ```mermaid flowchart TD A[PFK Deficiency]:::outcome --> B[Glycolysis blocked]:::urgent B --> C[No ATP in muscle]:::urgent C --> D[Muscle necrosis during exercise]:::urgent D --> E[Myoglobin released]:::urgent E --> F[Myoglobinuria]:::outcome F --> G{Urine pH & Flow?}:::decision G -->|Acidic, low flow| H[Myoglobin precipitates in tubules]:::urgent G -->|Alkaline, high flow| I[Myoglobin stays soluble, excreted]:::action H --> J[Acute Tubular Necrosis]:::urgent I --> K[Renal protection]:::action ``` ## Why Aggressive Diuresis + Alkalinization (Option 1) is Correct **Key Point:** The immediate threat is **acute kidney injury from myoglobin precipitation**. Myoglobin is soluble in alkaline urine but precipitates in acidic urine, causing tubular obstruction and ATN. ### Mechanism of Protection: 1. **Sodium bicarbonate:** - Alkalinizes urine to pH > 6.5 - Keeps myoglobin in soluble form - Prevents tubular precipitation and obstruction 2. **Aggressive IV hydration + diuretics (furosemide):** - Maintains high urine flow (target: 200–300 mL/hr) - Dilutes myoglobin concentration in tubular fluid - Reduces contact time with tubular epithelium - Prevents volume depletion from rhabdomyolysis **High-Yield:** Myoglobin-induced AKI is **preventable** if urine is kept alkaline and dilute. This is the standard of care for rhabdomyolysis (from any cause) in the first 24–48 hours. ### Monitoring: - Serum creatinine, BUN, potassium (hyperkalemia risk from muscle breakdown) - Urine myoglobin and color - Urine pH (maintain > 6.5) - Urine output (maintain > 200 mL/hr) ## Why Other Options Fail | Option | Problem | |--------|----------| | IV dextrose alone (Option 2) | Dextrose does NOT address the immediate AKI risk; myoglobin will still precipitate in acidic urine without alkalinization | | Muscle biopsy (Option 3) | Diagnostic, not therapeutic; wastes critical time; diagnosis is clinical + genetic testing; biopsy risks further muscle trauma | | Hemodialysis (Option 4) | Premature; reserved for refractory hyperkalemia, severe AKI, or fluid overload; not the immediate first-line step | **Clinical Pearl:** PFK deficiency is unique among glycogenoses because it presents with **exercise-induced myoglobinuria** rather than hepatomegaly or hypoglycemia. Patients must avoid strenuous exercise and maintain hydration. **Mnemonic:** **HALT** myoglobin-induced AKI: - **H**ydration (IV fluids) - **A**lkalinization (bicarbonate) - **L**ow urine concentration (diuretics) - **T**reat hyperkalemia if present ## Long-Term Management - Genetic counseling - Avoid strenuous exercise - Maintain hydration during activity - Educate on warning signs (myalgia, dark urine, weakness) - Consider high-carbohydrate diet (some benefit from glucose supplementation during exercise) [cite:Robbins 10e Ch 7; Harrison 21e Ch 297; KD Tripathi 8e Ch 12]