THALASSEMIA: INSIGHTS INTO GENETIC DETERMINANTS AND PATHOPHYSIOLOGICAL CONSEQUENCES

Abstract

Thalassemia is a heterogeneous group of hereditary hematological disorders characterized by various errors in globin-chain synthesis, leading to chronic anemia and multisystem involvement. The basic pathophysiology depends on the subtype: β-thalassemia most often involves mutations, rarely deletions, of the β-globin gene on chromosome 11; α-thalassemia is most commonly due to deletions involving the HBA1 and HBA2 genes or the surrounding regulatory regions. These genetic defects disturb the balance between the production of α- and β-globin chains, ultimately leading to ineffective erythropoiesis, hemolysis, iron overload, and a wide range of bone deformities and cardiometabolic complications. Further, myelofibrosis, vitamin B12 deficiency, porphyria cutanea tarda, increased liver enzymes, left ventricular hypertrophy, and chronic thromboembolic pulmonary hypertension are some of the secondary diseases associated with thalassemia, increasing its clinical spectrum even more. Advanced molecular diagnosis and detailed hematological investigations are crucial for better early detection and characterization of mutations. Treatment options include regular blood transfusions, hydroxyurea, and iron chelation to prevent organ injury, whereas newer thalidomide, sirolimus, antioxidant supplementation, bone marrow transplantation, and gene-based therapies hold promise for long-term disease modification. The combined review brings forth various complex pathophysiological mechanisms, diagnostic modalities, and changing treatment approaches that go on improving outcomes in patients with thalassemia.