Thalassemia

Thalassemias are a group of inherited hemoglobin disorders characterized by reduced or absent synthesis of one or more globin chains, leading to imbalanced globin production, ineffective erythropoiesis, and chronic hemolytic anemia. Normal adult hemoglobin (HbA) consists of two alpha and two beta globin chains (α2β2). Alpha-thalassemia results from gene deletions on chromosome 16 (four alpha-globin genes total, two per chromosome), while beta-thalassemia results from point mutations on chromosome 11 affecting beta-globin gene expression. Alpha-thalassemia severity depends on the number of deleted alpha genes: silent carrier (1 deletion, -α/αα, clinically normal), alpha-thalassemia trait (2 deletions, either -α/-α cis or -α/αα trans, mild microcytic anemia), HbH disease (3 deletions, --/-α, moderate hemolytic anemia with HbH [β4 tetramers] on electrophoresis), and hydrops fetalis/Hb Bart's (4 deletions, --/--, incompatible with life — Hb Bart's [γ4] has extreme oxygen affinity and cannot deliver O2 to tissues). Beta-thalassemia is classified as minor/trait (one defective beta gene, β/β+ or β/β0, mild microcytic anemia), intermedia (moderate disease, variable genotypes), and major (Cooley anemia, β0/β0 or severe β+/β0, transfusion-dependent). In beta-thalassemia major, excess unpaired alpha chains precipitate within erythroid...