In thalassemia major, what is the basic hematological defect?

In thalassemia major, the fundamental hematological defect lies in the synthesis of the β-chain of hemoglobin. This condition is primarily due to mutations in the HBB gene, which encodes the β-globin subunit of hemoglobin. As a result of these mutations, there is reduced or absent production of β-globin chains, leading to an imbalance in globin chain production.

In a healthy individual, hemoglobin consists of two alpha and two beta chains. However, in individuals with thalassemia major, the inadequate β-chain synthesis results in excess alpha chains, which can precipitate and form ineffective hemoglobin. This imbalance leads to ineffective erythropoiesis and hemolysis, causing severe anemia and requiring regular blood transfusions to manage the condition.

Understanding this defect is crucial, as it informs the clinical management and treatment of patients with thalassemia major, highlighting the importance of monitoring hemoglobin levels and the need for potential therapies such as gene therapy or bone marrow transplantation to address the underlying issue.