Sickle Cell Disease Case Study

Sickle cell disease (SCD) is a monogenic disorders (Bhanushali et al., 2014) characterized by chronic hemolytic anemia, acute vaso-occulusive crises (Platt, 2008), and the acute chest syndrome (ACS) (Lettre et al., 2008). A point mutation in the β-globin gene, the substitution of valine for glutamic acid at position 6 of the β-globin gene (Glu6Val), is the major cause of sickle cell anemia (Platt, 2008; Mtatiro et al., 2015). The mutated β-globin gene (Glu6Val) leads to the formation of sickle hemoglobin (HbS), a protein that when deoxygenated tends to polymerize into long fibers, thereby damaging the erythrocyte membrane and reducing it’s deformability (Platt, 2008; Ma et al., 2007). Since, the polymerization is directly proportional with …show more content…
The second mechanism is by directly enhance the fetal hemoglobin production due to that during the metabolism of hydroxyurea there is a huge amount of nitric oxide where produced and lead to the stimulation of heme iron containing enzyme, soluble guanylate cyclase, and as a result of this reaction a fetal hemoglobin will produced (Platt, 2008). Therefore, hydroxyurea overcome the bad effects of sickle hemoglobin (HbS), which causes a damage of the cell membrane by different ways leads to hemolysis and the loss of endogenous nitric oxide, on red blood cells (Platt, 2008). Hydroxyurea had excellent oral bioavailability and a half-life ranging from 2-4 hours which means a relatively rapid clearance in both adult and children (Ware et al., 2002). Also, it found to increase fetal hemoglobin (HbF) concentration from 10% to 40% when administered at maximum tolerated dose (MTD) (Ware et al., 2002; Iolascon et al.,