International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 193-202 http://medscipublisher.com/index.php/ijmms 194 2 Overview of Sickle Cell Anemia 2.1 Genetic and molecular basis Sickle cell anemia (SCA) is a hereditary blood disorder caused by a single nucleotide mutation in the beta-globin gene (HBB), resulting in the production of abnormal hemoglobin known as hemoglobin S (HbS) (DeWitt et al., 2016; Lin et al., 2017; Cisneros and Thein, 2020; Quagliano et al., 2022). This mutation leads to the polymerization of HbS under low oxygen conditions, causing red blood cells to deform into a sickle shape. These sickle-shaped cells are less flexible and can obstruct blood flow, leading to various complications (Figure 1) (DeWitt et al., 2016; Newby et al., 2021; Wilkinson et al., 2021). The discovery of the BCL11A gene, a major repressor of the γ-globin gene, has been pivotal in understanding the switch from fetal hemoglobin (HbF) to adult hemoglobin, providing new avenues for therapeutic intervention (Cisneros and Thein, 2020; Frangoul et al., 2020; Quagliano et al., 2022). Figure 1 Pathophysiology, inflammatory stimuli, and cellular interactions in SCA (Adopted from Wilkinson et al., 2021) Image caption: This figure illustrates the pathophysiology, inflammatory stimuli, and cellular interactions in Sickle Cell Anemia (SCA) (Adopted from Wilkinson et al., 2021) 2.2 Pathophysiology and symptoms The pathophysiology of SCA is primarily driven by the sickling of red blood cells, which leads to vaso-occlusion, hemolysis, and chronic inflammation (DeWitt et al., 2016; Frangoul et al., 2020). These processes result in severe pain crises, known as vaso-occlusive episodes, and progressive organ damage. Common symptoms include anemia, episodes of pain, swelling in the hands and feet, frequent infections, and delayed growth in children (Cisneros and Thein, 2020; Frangoul et al., 2020). The chronic hemolysis also leads to complications such as jaundice, gallstones, and an increased risk of stroke (Randolph and Zhao, 2015; DeWitt et al., 2016). 2.3 Epidemiology and global impact Sickle cell anemia predominantly affects individuals of African, Mediterranean, Middle Eastern, and Indian ancestry, with the highest prevalence in sub-Saharan Africa (Romero et al., 2018; Frangoul et al., 2020). It is estimated that millions of people worldwide are affected by SCA, with approximately 300,000 infants born with the condition each year (Randolph and Zhao, 2015; Frangoul et al., 2020). The disease poses a significant public health challenge, particularly in low-resource settings where access to comprehensive care and curative treatments like hematopoietic stem cell transplantation (HSCT) is limited (Romero et al., 2018; Lin et al., 2019). The global burden of SCA includes high morbidity and mortality rates, with many patients experiencing a reduced quality of life and life expectancy (Romero et al., 2018; Frangoul et al., 2020).
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