Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches.

Sickle cell disease (SCD) is an inherited blood disorder marked by the production of abnormal hemoglobin, leading to the distortion-or sickling-of red blood cells. The SCD arises from a single-point mutation that substitutes glutamic acid with valine at the sixth codon of the β-globin chain in hemoglobin. This substitution promotes deoxyhemoglobin aggregation, elevating red blood cell stiffness, and triggering vaso-occlusive and hemolytic repercussions.