A child presents with anemia after splenectomy and cholecystectomy. Labs show low hemoglobin, normal MCV, an increased reticulocyte count, and peripheral smear with pale red cells. What underlying defect is most likely?

• A. Hemoglobin S mutation
• B. G6PD deficiency
• C. Erythrocyte spectrin
• D. Pyruvate kinase deficiency

Answer: (C)

This scenario points to a membrane skeleton defect in red blood cells, causing hereditary spherocytosis. When the membrane cytoskeleton—especially proteins like spectrin that link the lipid bilayer to the internal cytoskeleton—is defective, the red cells lose membrane surface area and become spherical. Spherocytes are things the spleen recognizes and destroys, leading to extravascular hemolysis. That explains the anemia with a normal mean corpuscular volume, a brisk reticulocytosis as the bone marrow tries to compensate, and the pigmented gallstones that often prompt cholecystectomy. Splenectomy reduces the premature destruction of these abnormal cells, which is why this history fits well.

Among the proteins involved, spectrin is the classic defective component in this condition, so the underlying defect is in erythrocyte spectrin.