A 30-year-old Southeast Asian woman has Hb 7.2 g/dL, MCV 65 fL, splenomegaly, and jaundice. Iron studies are normal. Peripheral smear shows target cells and basophilic stippling. HPLC shows Hb H 8%, HbA2 2%. What is the underlying genetic defect?
- A Deletion of all four alpha-globin genes
- B Point mutations in the beta-globin gene
- C Deletion of three alpha-globin genes ✓
- D Mutations in the spectrin gene
Correct answer: C. Deletion of three alpha-globin genes
Explanation
Hb H disease results from deletion of three alpha-globin genes, leaving one functional alpha gene. This produces excess beta tetramers (Hb H) that precipitate and cause hemolysis. Deletion of all four alpha genes causes Hb Bart's hydrops fetalis, which is usually fatal in utero. Beta-globin mutations cause beta-thalassemia, and spectrin mutations cause hereditary spherocytosis.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.