A 35-year-old woman of Mediterranean descent has hemolytic anemia, splenomegaly, and HbH inclusions on brilliant cresyl blue staining. Hemoglobin electrophoresis shows no HbA, elevated HbH (β4), and trace HbBart (γ4). Genetic testing would most likely show:
- A Deletion of three alpha-globin genes (--/-α genotype) — HbH disease ✓
- B Deletion of all four alpha-globin genes (--/-- genotype) — Hb Bart's hydrops fetalis
- C Deletion of two alpha-globin genes in cis (--/αα genotype) — alpha thalassemia trait (Southeast Asian type)
- D A single alpha-globin gene deletion (-α/αα) — silent carrier
Explanation
HbH disease results from deletion of three of the four alpha-globin genes (--/-α genotype). With only one functional alpha-globin gene, excess beta chains form tetramers (HbH = β4) that precipitate as Heinz body-like inclusions visible with brilliant cresyl blue stain. HbBart (γ4) may be present in small amounts. Clinically: moderately severe hemolytic anemia and splenomegaly. Loss of all four alpha genes causes Hb Bart's hydrops fetalis (uniformly fatal in utero without intervention). Two-gene deletion causes thalassemia minor. Single deletion causes the silent carrier state.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.