A 28-year-old man of Southeast Asian origin has moderate hemolytic anemia with splenomegaly. Hemoglobin electrophoresis shows a fast-migrating fraction accounting for 15% of total hemoglobin, and supravital staining with brilliant cresyl blue reveals punctate inclusions in many red cells. The underlying defect involves:
- A Deletion of three alpha globin genes with excess beta chains forming tetramers ✓
- B Deletion of all four alpha globin genes
- C Point mutation producing HbS polymerization
- D Single alpha globin gene deletion with minimal hematologic effect
Correct answer: A. Deletion of three alpha globin genes with excess beta chains forming tetramers
Explanation
Hemoglobin H disease results from deletion of three of four alpha globin genes. The excess beta chains form soluble beta-4 tetramers (HbH) that precipitate as inclusions visible with brilliant cresyl blue, giving the classic golf-ball appearance. All four deletions cause gamma-4 (Hb Bart's) hydrops fetalis, incompatible with survival, while one or two deletions produce silent carrier state or alpha-thalassemia trait without significant inclusions.
Reference: Williams Hematology, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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