A 32-year-old woman of Mediterranean origin has haemolytic anaemia with haemoglobin 9.2 g/dL. Blood film shows target cells, hypochromic microcytic red cells, and no spherocytes. HPLC shows HbA 72%, HbA2 5.8%, HbF 1.5%. Her husband is found to have HbA 93%, HbA2 5.5%, HbF 1.5%. What is the risk to their offspring of having transfusion-dependent thalassaemia?

• A 50% risk of beta-thalassaemia intermedia
• B 25% risk of beta-thalassaemia major ✓
• C No significant risk; both parents have beta-thalassaemia trait which is clinically benign
• D 100% risk of beta-thalassaemia minor; no risk of major

Explanation

Both parents have beta-thalassaemia trait (minor) with characteristic elevated HbA2 >3.5% on HPLC, microcytic hypochromic anaemia, and normal HbF. Beta-thalassaemia trait is autosomal recessive (carrier = β/βo or β/β+ heterozygote). When both parents are carriers (β-thal trait), Mendelian inheritance predicts 25% chance of homozygous offspring (β-thal major — transfusion dependent), 50% chance of thalassaemia trait, and 25% chance of normal phenotype. Prenatal diagnosis by chorionic villus sampling or amniocentesis is recommended for couples where both are carriers.

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

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Written and medically reviewed by the StethoPrep medical team.