A 4-year-old girl of Mediterranean descent presents with severe pallor and hepatosplenomegaly. Peripheral smear shows target cells, nucleated RBCs, and hypochromia. Hb electrophoresis shows HbF 92%, HbA2 5%, no HbA. The diagnosis is:

• A Sickle cell anaemia
• B HbH disease (alpha thalassaemia)
• C Hereditary spherocytosis
• D Beta-thalassaemia major (Cooley's anaemia) ✓

Explanation

Beta-thalassaemia major is characterised by absent or severely reduced beta-globin chains; the compensation results in massive HbF elevation (80–95%), elevated HbA2 (>3.5%), and absent or near-absent HbA. Clinical presentation begins after 6 months when the switch from gamma to beta globin synthesis normally occurs, manifesting as severe transfusion-dependent anaemia with hepatosplenomegaly and bone marrow expansion. Sickle cell anaemia shows predominantly HbS on electrophoresis. HbH disease is alpha-thalassaemia with HbH (beta-4 tetramers). Hereditary spherocytosis shows spherocytes, not target cells, and normal electrophoresis.

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

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Written and medically reviewed by the StethoPrep medical team.