A 28-year-old woman of Mediterranean origin is found to have Hb 9.2 g/dL, MCV 62 fL, MCH 18 pg. HPLC shows HbA2 5.8%, HbF 3.2%, HbA 91%. Iron studies are normal. Her husband has HbA2 3.8% on HPLC. What is the risk to their offspring of having transfusion-dependent thalassemia (beta-thalassemia major)?

• A 0% — both parents are thalassemia trait and the offspring will only have trait
• B 50% per pregnancy — as only the mother is a carrier
• C 100% — as the mother has thalassemia intermedia
• D 25% per pregnancy — both parents carry one defective beta-globin allele ✓

Explanation

Beta-thalassemia trait (carrier state) is confirmed by elevated HbA2 >3.5% on HPLC. Both the woman (HbA2 5.8%) and her husband (HbA2 3.8%) are beta-thalassemia trait carriers. Each carries one normal and one defective beta-globin allele (beta/beta+). Autosomal recessive inheritance: with two carriers, each pregnancy has a 25% chance of inheriting both defective alleles (beta+/beta+ or beta0/beta0) resulting in beta-thalassemia major or severe thalassemia intermedia, 50% trait, and 25% normal. Prenatal diagnosis (CVS or amniocentesis with molecular analysis) should be offered at each pregnancy.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.