sickle cell disease,pathogenesis, sign andsymtoms

Sickle cell disease results from a single glutamic acid to valine substitution at position 6 of beta globin polypeptide chain. It is inherited as an autosomal recessive trait. Homozygotes only produce abnormal beta chains that make hemoglobin S and results in clinical syndrome of sickle cell disease. Heterozygotes produce a mixture of normal and abnormal beta chains that make normal HbA and HbS , hence results in the clinically asymptomatic sickle cell trait.Epidemiology:Individuals with sickle cell trait are relatively resisitant to the lethal effect of falciparum malaria in early childhood. So it provides survival advantage in Africa.Pathogenesis of Sickle cell disease:When heamoglobin S is deoxygenated, the molecules of haemoglobin polymerase to form pseudocrystalline structures known as tactoids. These distort the red cell membrane and produce characteristic sickle shaped cells. The polymerization is reversible when reoxygenation occurs. The distortion of the red cell membrane however may become permanent, and the redcell irreversibly sickled. The greater the concentration of sickle cell heamoglobin in the individual cells, the more easy tactoids are formed, but this procedd may be enhanced or retarded by the presence of other haemoglobins. Thus haemoglobin C participates in the polymerization more readily than haemoglobin A, where as haemoglobin F strongly inhibits polymerization.to