Thalassemia

Thalassemia is an autosomal recessive hemoglobinopathy caused by mutations in genes encoding alpha or beta globin chains, resulting in reduced or absent hemoglobin production. The imbalance of globin chains causes hemolysis (destruction of red blood cells) and ineffective erythropoiesis (impaired red blood cell production). In beta-thalassemia major, the most severe form, hemoglobin production is virtually absent, resulting in severe hemolytic anemia requiring regular blood transfusions to maintain acceptable hemoglobin levels. Chronic transfusion leads to iron overload, causing organ damage (cirrhosis, cardiomyopathy, endocrine dysfunction). Extramedullary hematopoiesis (blood production outside the bone marrow) causes hepatosplenomegaly and bone expansion with characteristic facial deformities. Without transfusion and iron chelation therapy, death typically occurs in childhood. Alpha-thalassemia has variable presentations depending on the number of alpha-globin genes deleted.