Thalassemia

Thalassemia is an inherited disorder of hemoglobin production. One or more globin chains are made in insufficient amounts, so developing red blood cells receive an imbalanced set of building blocks. Many precursors die in the bone marrow before reaching circulation; the cells that do circulate are fragile and undergo premature hemolysis. The result is a combination of ineffective erythropoiesis and chronic hemolytic anemia. Alpha-thalassemia usually reflects deletion or inactivation of alpha-globin genes. Disease severity increases as more of the four alpha-globin copies are affected: one affected copy may produce a clinically silent carrier state, two often produce a mild microcytic anemia, and three can cause hemoglobin H disease with clinically significant hemolysis. Loss of all four copies causes severe fetal anemia and hydrops fetalis. Beta-thalassemia results from mutations that reduce or eliminate beta-globin production. One affected beta-globin gene commonly produces beta-thalassemia trait, which is usually mild. More severe beta-thalassemia can cause chronic anemia, splenomegaly, growth impairment, and transfusion dependence beginning in childhood. The marrow responds to chronic anemia by expanding erythroid tissue and releasing signals that increase erythropoietic activity. In...