A 28-year-old Indian male presents to the emergency department with severe hemolytic anemia following consumption of fava beans. Laboratory investigations reveal hemoglobin 7.2 g/dL, reticulocyte count 8.5%, and elevated indirect bilirubin. Peripheral blood smear shows Heinz bodies. Urine dipstick is positive for blood but RBCs are absent. Which of the following enzyme deficiencies is most likely responsible for this clinical presentation?

Explanation

## Clinical Diagnosis: G6PD Deficiency ### Pathophysiology of the Presentation **Key Point:** G6PD deficiency impairs the pentose phosphate pathway's oxidative phase, reducing NADPH production and compromising the antioxidant defense system (glutathione reduction cycle). Fava beans contain **divicine** and **isouramil**, oxidative stressors that trigger hemolysis in G6PD-deficient individuals. Without adequate NADPH, reduced glutathione (GSH) cannot be regenerated, leading to: 1. Accumulation of reactive oxygen species (ROS) 2. Oxidative damage to RBC membranes and hemoglobin 3. Formation of Heinz bodies (denatured hemoglobin precipitates) 4. Hemolysis and hemoglobinuria (positive dipstick without RBCs) ### Pentose Phosphate Pathway Role ```mermaid flowchart TD A[Glucose-6-phosphate]:::action --> B[G6PD catalyzes oxidative phase]:::action B --> C[NADPH production]:::action C --> D[GSH reduction cycle activated]:::action D --> E[ROS neutralized]:::outcome F[G6PD deficiency] --> G[Reduced NADPH]:::urgent G --> H[GSH remains oxidized]:::urgent H --> I[ROS accumulates]:::urgent I --> J[Hemolysis, Heinz bodies]:::urgent ``` ### Key Laboratory Findings in G6PD Deficiency | Finding | Mechanism | Significance | |---------|-----------|-------------| | Heinz bodies | Denatured Hb precipitates | Pathognomonic for oxidative hemolysis | | Hemoglobinuria (positive dipstick, no RBCs) | Free Hb in urine | Indicates intravascular hemolysis | | Elevated reticulocyte count | Compensatory RBC production | Indicates ongoing hemolysis | | Elevated indirect bilirubin | Hb breakdown product | Unconjugated hyperbilirubinemia | **High-Yield:** G6PD deficiency is the most common enzyme deficiency worldwide, affecting ~400 million people, particularly those of African and Mediterranean descent. It is X-linked recessive. **Clinical Pearl:** The diagnosis is confirmed by G6PD enzyme assay (must be done during remission, not acute hemolysis, as reticulocytes have higher enzyme levels and may falsely normalize results). [cite:Lehninger Principles of Biochemistry Ch 20]