The compound state: Hb S/beta-thalassemia☆

Sickle cell disease (SCD) results from a single amino acid substitution in the gene encoding the -globin subunit ( 6Glu > Val) that produces the abnormal hemoglobin (Hb) named Hb S. SCD has different genotypes with substantial variations in presentation and clinical course (Table 1).1,2 The combination of the sickle cell mutation and beta-thalassemia ( -Thal) mutation gives rise to a compound heterozygous condition known as Hb S/ thalassemia (Hb S/ -Thal), which was first described in 1944 by Silvestroni and Bianco.3 The polymerization of deoxygenated Hb S (sickling) is the primary event in the molecular pathogenesis of SCD. However, this event is highly dependent on the intracellular Hb composition; in other words, it is dependent on the concentration of Hb S, and type and concentration of the other types of Hb. Therefore, the major primary genetic determinant of the severity of SCD is the genotype.2,4–6 Many different -Thal mutations have been associated with Hb S, and the molecular basis of the thalassemia in Hb S/ -Thal individuals reflects the spectrum of -Thal mutations observed in a particular population.5,7–12 The heterogeneity of the -Thal mutations leads to quantitatively different -globin synthesis and consequently to different amounts of Hb A. This fact results in variable clinical manifestations, ranging from nearly asymptomatic to a severe condition similar to sickle cell anemia (homozygous Hb S).3,13 There is no consensus about the classification of Hb S/ -Thal, but it is usually classified in two types: Hb S/ 0-Thal and Hb S/ +-Thal.2,4 Hb S/ 0-Thal, in which the production of Hb A is abolished, is often clinically indistinguishable from sickle cell anemia. The thalassemia acts on sickled red blood cells, inducing microcytosis, hypochromia, and sometimes Hb F is elevated. This result in an improvement of the circulatory competence of these cells, a reduction of hemolysis, and a