A neonate presents with severe hemolytic anemia, hydrops fetalis, and a peripheral blood smear showing numerous nucleated red cells but very few normal erythrocytes. Hemoglobin electrophoresis shows almost exclusively Hb Barts (γ4). The genetic basis is:
- A Deletion of three alpha-globin genes (−−/−α)
- B Deletion of all four alpha-globin genes (−−/−−) ✓
- C Beta-thalassemia major (β0/β0)
- D HbH disease (deletion of two alpha-globin genes on same chromosome)
Correct answer: B. Deletion of all four alpha-globin genes (−−/−−)
Explanation
Hb Barts hydrops fetalis results from deletion of all four alpha-globin genes (homozygous alpha-thalassemia-1: −−/−−). Without any alpha chains, excess gamma chains form tetramers (γ4 = Hb Barts), which have extremely high oxygen affinity and fail to deliver oxygen to tissues, causing severe fetal hypoxia and hydrops. HbH disease (−−/−α) has only mild-moderate hemolysis. Beta-thalassemia major affects beta chains, not alpha, and presents later in life.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.