A 32-year-old woman of South Indian origin presents with jaundice, dark urine, and mild abdominal pain for 2 days. She reports a history of similar episodes triggered by infections or fava bean consumption. On examination, she is icteric with mild splenomegaly. Laboratory findings: Hb 9.2 g/dL, reticulocyte count 8.5%, indirect bilirubin 4.2 mg/dL, LDH 680 U/L, haptoglobin <10 mg/dL. Peripheral blood smear shows bite cells and polychromasia. What is the most likely diagnosis?

Explanation

## Diagnosis: G6PD Deficiency **Key Point:** G6PD deficiency is an X-linked enzymopathy affecting the pentose phosphate pathway, making RBCs vulnerable to oxidative stress. Acute hemolytic episodes are triggered by infection, drugs (sulfonamides, aspirin, antimalarials), or fava bean ingestion. ### Clinical Clues in This Case 1. **Demographic:** South Indian woman (high prevalence in Mediterranean, African, and Asian populations) 2. **Trigger history:** Fava bean consumption explicitly mentioned 3. **Acute hemolytic episode:** Jaundice, dark urine, elevated indirect bilirubin, high LDH, low haptoglobin 4. **Reticulocytosis:** 8.5% indicates appropriate bone marrow response 5. **Bite cells on smear:** Pathognomonic finding—Heinz bodies are removed by splenic macrophages, leaving "bite" marks on RBC membrane ### Pathophysiology ```mermaid flowchart TD A[G6PD Enzyme Deficiency]:::outcome --> B[Reduced NADPH production]:::outcome B --> C[Impaired antioxidant defense]:::outcome C --> D[Oxidative stress from trigger]:::decision D -->|Infection, drugs, fava beans| E[Hemoglobin denaturation]:::outcome E --> F[Heinz body formation]:::outcome F --> G[Splenic removal → Bite cells]:::outcome G --> H[Acute hemolytic anemia]:::urgent ``` ### Diagnostic Confirmation - **Heinz body stain:** Precipitated denatured hemoglobin (supravital stain) - **Bite cells:** RBCs with membrane defects after Heinz body removal - **G6PD enzyme assay:** Gold standard; may be falsely normal during acute hemolysis (young RBCs have higher enzyme levels) - **Osmotic fragility test:** Normal (rules out HS) **High-Yield:** G6PD deficiency is **episodic**, not chronic hemolysis. Between episodes, Hb and reticulocyte count normalize. Hereditary spherocytosis causes **chronic** hemolysis with persistent reticulocytosis. **Clinical Pearl:** In acute hemolytic crisis, enzyme assay may be falsely reassuring because reticulocytes (which predominate) have higher G6PD levels. Repeat testing 3–4 weeks post-crisis for accurate diagnosis. [cite:Robbins 10e Ch 13]