Sickle cell disease

Abstract

Sickle cell disease (SCD) is the most common monogenic disorder and its prevalence is high throughout large areas in sub-Saharan Africa, the Mediterranean basin, the Middle East and India because of the remarkable level of protection that the sickle cell trait provides against malaria. This stems from a selection pressure, in fact high frequencies of the variant gene correspond to areas of high malarial transmission. It is estimated that approximately 300,000 babies per year are born with sickle cell anaemia. SCD is an inherited haemoglobinopathy caused by a single amino acid substitution at the sixth residue of the beta-globin subunit (p.Glu6Val) resulting in the production of the characteristic haemoglobin S (HbS). Under deoxygenation conditions (when Hb is not bound to oxygen), the haemoglobin tetramers, that include the two-mutant sickle 13-globin subunits (HbS), can polymerize causing the erythrocyte to undertake a crescent or sickle cell shape. These sickle cell shaped RBCs are rigid and dysfunctional, and also play a central role in acute and chronic clinical manifestations of SCD. The increased adhesiveness of the sickle cells causes microvascular obstructions in capillaries giving rise to blockage of blood flow with ischaemic/reperfusion injury.