A 24-year-old man of West African ancestry is evaluated for mild chronic hemolysis and splenomegaly. Smear shows many target cells and occasional short hexagonal rod-like inclusions within red cells. Hemoglobin electrophoresis shows a slow-moving band accounting for 90% of total hemoglobin. The underlying defect involves substitution of which amino acid?

• A Glutamic acid replaced by lysine at position 6 of beta globin ✓
• B Valine replaced by glutamic acid at position 6 of beta globin
• C Glutamic acid replaced by valine at position 6 of beta globin
• D Lysine replaced by glutamine at position 26 of beta globin

Explanation

Hemoglobin C results from a Glu-to-Lys substitution at codon 6 of the beta globin gene, the same position mutated in HbS but with a different residue. Reduced solubility leads to intraerythrocytic HbC crystals, target cells, and mild extravascular hemolysis; homozygous HbC disease is much milder than sickle cell disease. HbS is Glu-to-Val at position 6. HbE is Glu-to-Lys at codon 26 and produces microcytosis rather than crystallization.

Reference: Williams Hematology, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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