How benign is sickle cell trait?

The complications of sickle cell disease (SCD) arise from the presence in red cells of the mutated haemoglobin, HbS, which replaces the normal adult Hb,HbA. HbS has a single amino acid substitutionwhereby valine replaces glutamic acid in the 6th codon of the β chain. Most SCD patients inherit two copies of the sickle gene (homozygous HbSS individuals sometimes termed sickle cell anaemia, SCA). About a third of SCD patients co-inherit HbS with a second abnormal Hb, HbC, in which lysine replaces glutamic acid in the same codon (heterozygous HbSC individuals). There are also a number of rarer genotypes of SCD such as HbS/β thalassaemia. The initial event in pathogenesis of SCD is the ability of the neighbouring molecules of HbS to aggregate into long, rigid polymers following deoxygenation. There are multiple sequelae including altered red cell rheology, fragility, increased cation permeability and stickiness. These events result in the two main complications of SCD, a chronic anaemia and acute episodes of ischaemia, which can elicit pain and also damage multiple tissues in organs including the brain, lungs, bones and kidney. Sickle cell trait (SCT) individuals inherit one copy of HbA and one of HbS (HbAS). The selection pressure for HbS lies in the relative protection of these heterozygotes from the severest form of malaria, Plasmodium falciparum. There are hundreds of millions SCT individuals worldwide. About 9% blacks (3 million people), 0.2% Caucasians and 1.5% babies in USA have SCT. In the UK, there are about a quarter of a million individualswith SCT. Prevalence is even higher in areas endemic formalaria, with SCT reaching around 25% in someparts of Africa and up