Sickle Cell Anemia is a common autosomal recessive disorder resulting from the production of a variant hemoglobin called HbS (sickle cell hemoglobin).
It is typically caused by a point mutation in the beta-globin gene at residue 6, Glu →Val (GAG→ GTG) causing a loss of a negative charge and a decreased solubility of the mutant Hb (HbS). Under low oxygen tension, HbS aggregate (polymerizes in rod shaped form), distorting the shape of the RBC to sickle shape. This misshapen RBC is unable to squeeze through capillaries causing vascular occlusion and consequently local hypoxia or hemolysis.
Because sickle cell anemia is an autosomal recessive condition, in order for a child to get it, they can inherit it from either one or both of their parents, and in the former case, they will be a carrier and will exhibit sickle cell trait (e.g., only some blood cells are sickled). In the latter case, all their RBCs will be sickled. In places such as Africa where Malaria (plasmodium falciparum) is quite prevalent, sickle cell trait provides a selective advantage for carriers.
Some common symptoms are:
Anemia (Hb level 6-10 g/dL)
Failure to thrive
Splenomegaly
Repeated infection
Painful swelling of hands or feet (from occlusion of capillaries)
Infection major cause of death