Alpha-thalassemia is an autosomal recessive hematologic disorder caused by deletion mutations in the four alpha-globin genes (two per copy of chromosome 16) required for normal hemoglobin synthesis, in which hemoglobin is a tetrameric protein composed of paired globin chains (alpha, beta, gamma, delta) whose combinations form distinct hemoglobin types (fetal, adult major, adult minor). Disease severity scales directly with the number of deleted alpha genes, ranging from an asymptomatic silent-carrier state (one gene) through mild anemia (two genes, via cis or trans deletion patterns), moderate hemolytic anemia from pathological beta-chain tetramer formation (three genes, hemoglobin H disease), to a lethal fetal syndrome driven by high-oxygen-affinity gamma-chain tetramers causing severe hypoxia and hydrops fetalis (four genes); the underlying mechanism in each case is an imbalance in globin chain stoichiometry leading to compensatory abnormal tetramer formation, hemolysis, and tissue hypoxia.
Alpha-thalassemia is an autosomal recessive hematologic disorder caused by deletion mutations in the four alpha-globin genes (two per copy of chromosome 16) required for normal hemoglobin synthesis, …