A 25-year-old man of Southeast Asian origin has lifelong moderate anemia with splenomegaly. Hb 8.2 g/L equivalent noted as 8.2 g/dL, MCV 54 fL, iron studies normal. Smear shows striking microcytosis, target cells, and basophilic stippling. Supravital staining of blood reveals numerous red cell inclusions. Electrophoresis shows 12% of a fast-migrating hemoglobin band. What is the defect?
- A Deletion of one alpha globin gene (silent carrier state)
- B Single beta globin gene mutation causing beta-thalassemia intermedia
- C Deletion of three alpha globin genes causing HbH disease ✓
- D Homozygous hereditary persistence of fetal hemoglobin
Correct answer: C. Deletion of three alpha globin genes causing HbH disease
Explanation
Three deleted alpha genes leave only one functional alpha locus, so excess beta chains form beta4 tetramers (hemoglobin H), a fast-migrating band on electrophoresis that precipitates as red cell inclusions visible on supravital stains such as brilliant cresyl blue. One deleted gene is clinically silent, and HPFH produces high HbF without inclusions. Normal iron studies exclude iron-related microcytosis.
Reference: Williams Hematology, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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