For SCD, there is a basic scheme that can be used to simplify the explanation of its pathogenesis: SCD severity generally correlates with the degree to which sickling occurs in the blood of patients. Also, the quantity of sickled RBCs in the circulation typically reflects the amount of mutant Hb S protein in RBCs.
The Hb S protein differs by only a single amino acid from the normal Hb
protein. This single amino acid difference that is present in the Hb S molecule
is the result of a single point mutation in the gene that codes for one of the Hb
proteins. Thus, the inheritance of this gene mutation is the primary underlying cause of SCD pathogenesis.