A 3-year-old boy from rural Maharashtra presents with recurrent infections, jaundice, and dark urine after eating fava beans. Blood smear shows bite cells and blister cells. Hemoglobin electrophoresis is normal. Which is the most appropriate immediate next step in management?

Explanation

## Clinical Context: G6PD Deficiency & Pentose Phosphate Pathway **Key Point:** This child presents with acute hemolytic anemia triggered by oxidative stress (fava bean exposure), with classic findings of G6PD deficiency: bite cells, blister cells, and jaundice. ### Why G6PD Enzyme Activity Measurement is the Next Step G6PD catalyzes the first committed step of the pentose phosphate pathway (oxidative phase), generating NADPH. NADPH is the critical reducing cofactor that maintains glutathione in its reduced form (GSH), which protects RBCs from oxidative damage. **High-Yield:** In G6PD deficiency: - RBCs cannot generate sufficient NADPH during oxidative stress - Glutathione becomes oxidized (GSSG), and RBCs lose antioxidant defence - Hemoglobin denatures → Heinz bodies → bite cells (when splenic macrophages remove Heinz bodies) - Hemolysis occurs acutely with triggers: fava beans, sulfonamides, infections, aspirin ### Diagnostic Confirmation Algorithm ```mermaid flowchart TD A[Suspected G6PD deficiency<br/>Hemolytic episode + fava bean trigger]:::outcome --> B{Acute hemolysis<br/>confirmed?}:::decision B -->|Yes| C[Measure G6PD enzyme activity<br/>in RBCs]:::action C --> D{G6PD activity<br/>low?}:::decision D -->|Yes| E[Confirm G6PD deficiency<br/>Genetic testing if needed]:::outcome D -->|No| F[Consider other causes<br/>of hemolysis]:::outcome B -->|No| G[Supportive care only]:::action ``` **Clinical Pearl:** Enzyme assay should be performed after the acute hemolytic episode has resolved (2–3 weeks later), because reticulocytosis and young RBCs (which have higher G6PD activity) can falsely normalize the result during acute hemolysis. ### Management After Diagnosis 1. **Acute phase:** Supportive care (hydration, transfusion if Hb < 7 g/dL) 2. **Long-term:** Avoidance of triggers (fava beans, sulfonamides, NSAIDs, infections) 3. **No role for:** Splenectomy (not indicated; hemolysis is metabolic, not immune), corticosteroids (ineffective in G6PD), or routine transfusion (self-limited if triggers avoided) **Mnemonic:** **NADPH Protects RBCs** — NADPH (from PPP) → GSH reduction → Antioxidant defence → RBC survival