Synthesis of Globin Chains in Sickle β-Thalassemia

Abstract

In five patients with sickle β-thalassemia there was balanced α- and β-globin synthesis in the bone marrow and decreased total β-chain synthesis relative to that of α-chain in the peripheral blood. These findings are similar to those in patients with simple β-thalassemia trait. Despite a range of hemoglobin concentrations from 6.8 to 12.5 g/100 ml in the patients with sickle thalassemia, there was no evidence of a significant excess of α-chains in the red cells of the bone marrow which could contribute to the hemolysis and anemia. In patients heterozygous for β-thalassemia the capacity to synthesize β-chain decreases more rapidly than that for α-chain. In nonthalassemic subjects the rates of β- and α-chain synthesis decrease equally as the red cell matures. The β^S- and β^A-chains serve as convenient markers for globin synthesis due to the nonthalassemic and thalassemic alleles in patients with sickle β-thalassemia. The unbalanced globin synthesis in the peripheral blood of these patients is explained by the decrease in relative synthesis of β^S-chain, in comparison with that of α-chain. This instability is not present in sickle cell trait. The β^A-chain synthesis was only unstable in the two patients who had the most marked anemia. The major mechanism for achieving balanced globin production in the bone marrow in the presence of one thalassemic gene appears to be increased synthesis of β-chain due to the nonthalassemic allele. In addition, there may be a decrease of total α-chain synthesis in some patients.