A patient with hereditary spherocytosis shows osmotic fragility, spherocytes on smear, and negative direct Coombs test. The primary molecular defect in the most common form is deficiency of:

• A Pyruvate kinase
• B Glucose-6-phosphate dehydrogenase
• C Spectrin or ankyrin proteins ✓
• D Hexokinase

Explanation

Hereditary spherocytosis most commonly results from mutations in spectrin (alpha or beta) or ankyrin (the most common defect overall), disrupting the vertical linkage between the lipid bilayer and the cytoskeleton. This leads to membrane loss, decreased surface-to-volume ratio, spherocyte formation, and splenic trapping. Pyruvate kinase deficiency causes non-spherocytic hemolytic anemia. G6PD deficiency causes episodic oxidative hemolysis.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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