A 20-year-old woman of Mediterranean origin has chronic hemolytic anemia, splenomegaly, and indirect hyperbilirubinemia. Peripheral blood shows target cells, basophilic stippling, and nucleated RBCs. Hb electrophoresis: HbA 0%, HbF 95%, HbA2 5%. The molecular defect most likely involves:
- A Point mutation causing amino acid substitution in beta-globin chain
- B Deletion or mutation causing absent or markedly reduced beta-globin chain synthesis ✓
- C Alpha-globin gene deletions producing excess unpaired beta chains
- D Structural instability of the spectrin-ankyrin cytoskeletal network
Correct answer: B. Deletion or mutation causing absent or markedly reduced beta-globin chain synthesis
Explanation
HbA (α2β2) is absent (0%), HbF (α2γ2) is 95%, and HbA2 (α2δ2) is 5% — this pattern is beta-thalassemia major (β0/β0 or compound heterozygote). The molecular defect is in the beta-globin gene (various point mutations, small insertions/deletions affecting transcription, splicing, or translation), leading to absent (β0) or severely reduced (β+) beta-chain synthesis. Excess unpaired alpha chains precipitate, causing ineffective erythropoiesis. Alpha-thalassemia results from alpha-globin gene deletions producing HbH or Hb Barts.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.