Sickle Cell Disease

Sickle cell disease is an autosomal recessive hemoglobinopathy caused by a single nucleotide substitution in the beta-globin gene (GAG→GTG codon 6), resulting in glutamic acid→valine substitution that promotes hemoglobin polymerization under conditions of low oxygen tension. Under deoxygenation, hemoglobin S polymerizes into long fibers that distort red blood cells into rigid, sickle shapes. These sickled cells cause hemolysis (destroying red blood cells), leading to severe anemia and jaundice, and cause vaso-occlusion (blockade of blood vessels), leading to severe pain, organ infarction, and progressive organ damage. Pain crises are the hallmark of the disease and can be triggered by cold, infection, dehydration, or hypoxia. Acute chest syndrome (vaso-occlusion in the lungs) is life-threatening. Progressive organ damage causes kidney disease, stroke, cardiac disease, and avascular necrosis of bones. Although historically SCD was a serious threat to life expectancy, newer therapies including hydroxyurea, L-glutamine, and emerging gene therapies have dramatically improved outcomes.