A 28-year-old Indian woman presents with jaundice, dark urine, and fatigue for 3 days. She has a history of recurrent episodes of hemolysis triggered by infections and fava bean consumption. On examination, she is icteric with splenomegaly. Laboratory findings show: Hemoglobin 7.2 g/dL, reticulocyte count 12%, indirect bilirubin 4.8 mg/dL, LDH 680 U/L, haptoglobin <10 mg/dL. Peripheral blood smear shows bite cells and Heinz bodies on supravital staining. What is the most likely diagnosis?

Explanation

## Diagnosis: Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency ### Clinical Presentation The patient presents with acute hemolytic crisis triggered by infection and fava bean ingestion—classic precipitants of G6PD deficiency. The constellation of jaundice, dark urine, and splenomegaly in an acute hemolytic episode is characteristic. ### Pathophysiology **Key Point:** G6PD deficiency is an X-linked enzymopathy affecting the pentose phosphate pathway. RBCs lack protection against oxidative stress, leading to hemoglobin denaturation and hemolysis when exposed to oxidative triggers (infections, drugs, fava beans). ### Laboratory Findings—Diagnostic Clues | Finding | Interpretation | |---------|----------------| | **Bite cells** | RBCs with Heinz bodies removed by splenic macrophages; pathognomonic for G6PD | | **Heinz bodies** (supravital stain) | Denatured hemoglobin precipitates; seen only in G6PD and other hemoglobinopathies | | **Elevated reticulocyte count (12%)** | Brisk bone marrow response to hemolysis | | **Elevated LDH + low haptoglobin** | Confirms intravascular hemolysis | | **Indirect hyperbilirubinemia** | From accelerated RBC destruction | **High-Yield:** Bite cells + Heinz bodies on supravital staining = G6PD deficiency until proven otherwise. ### Definitive Diagnosis G6PD enzyme assay (spectrophotometric or fluorescent spot test) during or shortly after acute hemolytic episode. Note: enzyme levels may be falsely normal 2–3 weeks post-hemolysis due to reticulocytosis (young RBCs have higher enzyme activity). ### Management 1. **Acute phase:** Supportive care, hydration, blood transfusion if Hb <5 g/dL or symptomatic 2. **Chronic:** Avoidance of triggers (infections, fava beans, oxidative drugs: sulfonamides, aspirin, antimalarials) 3. **Counseling:** X-linked inheritance; affected males; carrier females may have variable hemolysis **Clinical Pearl:** G6PD is the most common enzyme deficiency worldwide (~400 million people), particularly in Mediterranean, African, and Asian populations. Neonatal jaundice is a common presentation in affected infants. [cite:Robbins 10e Ch 12]