Sickle Cell Disease

Sickle cell hemoglobin (HbS) results from a single nucleotide substitution which changes the codon of the sixth β-globin amino acid from glutamic acid to valine (GAG→GTG: Glu6Val) and is the causative agent of sickle cell disease when homozygous. Homozygotes have α₂^Aβ₂^S hemoglobin. Heterozygotes (said to have sickle cell trait) have α₂^Aβ₂^S (HbS), α₂^Aβ₂^A (HbA) and α₂^Aβ₂^Sβ₂^A (HbS/HbA hybrid) hemoglobin, and are clinically normal despite mild symptoms under low oxygen pressure. In Sickle Cell Disease, the HbS β chains form chains, aggregating into long fibers which deform the cell, impair its function and result in hemolysis for homozygotes.