Sickle Cell Disease: A Genetic Disorder of Beta-Globin

Abstract

Sickle cell disease (SCD) is a structural and monogenetic genetic disorder due to a mutation that occurs in the globin β-chain, resulting in the formation of hemoglobin S (Hb S), a protein composed of two normal, and two β-type mutant chains. Estimates indicate that the prevalence among live births is 4.4% in the world. The difficulty in circulating the sickle cell, its interaction with endothelial cells, leukocytes, platelets, endothelial dysfunction, and the abnormal expression of adhesion molecules permeate the beginning of the blood vessel occlusion process as well as pathophysiological aspects of SCD. Among the secondary complications are the stroke, pulmonary hypertension, leg ulcer, renal disorders, and all complications associated with vascular dysfunction. Clinical and biochemical markers of disease severity can be used to predict risk, prevent complications, and increase the expectation and quality of life of the SCD population. The entire scenario generated by Hb S has implications for the health and social inclusion of patients, so the treatment of the person with SCD needs an approach focused on the prevention of these complications in an individualized way.

Genome Editing in Translational Medicine: An Inventory

“…One of the most prominent examples includes two patients, one suffering from TDT and the other from SCD. Both diseases are caused by mutations in the β-globin (HBB) gene resulting in dysfunctional erythrocytes [99][100][101]. While adult hemoglobin consists of α and β chains, fetal hemoglobin consists of α and γ chains [99][100][101].…”

“…Both diseases are caused by mutations in the β-globin (HBB) gene resulting in dysfunctional erythrocytes [99][100][101]. While adult hemoglobin consists of α and β chains, fetal hemoglobin consists of α and γ chains [99][100][101]. During the course of development, γ-globin (HBG) gene expression declines, thus fetal hemoglobin levels are reduced [99][100][101].…”

“…While adult hemoglobin consists of α and β chains, fetal hemoglobin consists of α and γ chains [99][100][101]. During the course of development, γ-globin (HBG) gene expression declines, thus fetal hemoglobin levels are reduced [99][100][101]. Suppression of HBG expression is mediated by the transcription factor BCL11A [102,103].…”

Polymorphism and Association of the E-selectin and ICAM-1-K469E Genes with Sickle Cell Disease in Congo

“…Furthermore, it is estimated that approximately 52,000 Europeans and 100 000 Americans have SCD, but the number of patients with SCD in both continents are steadily increasing due to migration [3,4]. SCD is caused by the substitution of glutamic acid by valine at the sixth position of the beta globin chain of the hemoglobin molecule [5]. This results in a defective Hemoglobin molecule (HbS) which is unable to carry enough oxygen.…”

A Review on Significance of Moringa oleifera in the Treatment of Heme-Related Disorders and Malnutrition

“…Heme production is initiated prior to the synthesis of the globin protein. When valine is substituted for glutamic acid at the sixth position of haemoglobin's chain, a hydrophobic molecule is swapped out for a hydrophilic one, resulting in sickle cell disease (SCD) (Renaudier, 2014;Inusa et al 2019;Cordovil, 2018). In hypoxic settings, erythrocytes sickle due to a loss of electrical charge (Liu et al, 2019;Grygorczyk and Orlov, 2017;Xu et al, 2020).…”