A 30-year-old Mediterranean woman has chronic hemolytic anemia, splenomegaly, target cells, HbA2 6.5%, and HbF 45% on electrophoresis. The molecular defect is:
- A Beta-thalassemia major — severely reduced or absent beta-globin chain synthesis ✓
- B HbS — glutamate to valine substitution at beta-6
- C Alpha-thalassemia trait — deletion of two alpha-globin genes
- D HbC disease — glutamate to lysine substitution at beta-6
Correct answer: A. Beta-thalassemia major — severely reduced or absent beta-globin chain synthesis
Explanation
Beta-thalassemia major (Cooley anemia) shows severe reduction/absence of beta-globin chains, leading to excess alpha chains that precipitate and damage RBCs. Compensatory increase in HbF and HbA2 are characteristic, with HbA markedly reduced. HbS has Glu→Val at beta-6 causing sickling; HbC has Glu→Lys at beta-6 causing mild hemolysis; alpha-thalassemia trait does not cause elevated HbA2.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.