A 3-year-old boy presents with severe hemolytic anemia, hepatosplenomegaly, and bone marrow expansion causing frontal bossing ('hair-on-end' skull X-ray). Hemoglobin electrophoresis shows predominantly HbF with HbA2 in the normal range. The diagnosis is β-thalassemia major. The primary cause of ineffective erythropoiesis in this condition is:

• A Unpaired α-globin chains forming toxic intracellular inclusions that damage the erythroid precursors ✓
• B Excess β-globin chains precipitating in the cytoplasm
• C Deficient iron absorption causing hypochromic microcytic anemia
• D Autoimmune destruction of erythroid precursors

Explanation

In β-thalassemia major, absent/markedly reduced β-chain synthesis leaves excess unpaired α-globin chains, which are insoluble and precipitate as toxic intracellular inclusions in erythroid precursors in the bone marrow. This causes massive intramedullary destruction of erythroid precursors (ineffective erythropoiesis), leading to marrow expansion and bone deformities. The few surviving RBCs are destroyed by the spleen (hemolytic component). Excess α-chains also bind to spectrin, damaging the membrane.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.