A 22-year-old Southeast Asian man has thalassemia intermedia. Hemoglobin electrophoresis shows HbE 65%, HbF 30%, HbA 0%, HbA2 5%. Which genetic compound heterozygosity best explains this phenotype?
- A HbE/HbE homozygosity
- B HbE/HbS compound heterozygote
- C HbE/beta-thalassemia compound heterozygote ✓
- D Beta-thalassemia major (homozygous beta0)
Explanation
HbE/beta-thalassemia is the most common cause of thalassemia intermedia/major in Southeast Asia. HbE itself is a beta-chain variant (Glu26Lys) that also creates a splicing mutation, reducing normal beta-globin and producing a mildly unstable hemoglobin. When combined with a beta-thalassemia allele, total beta-globin output is severely reduced, resulting in HbE + HbF + residual HbA2 without HbA. Clinically it ranges from thalassemia intermedia to major depending on the severity of the coexisting beta-thalassemia allele. Homozygous HbE is mild; HbS/HbE produces a sickle-like disorder.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.