HBB

About HBB

HBB on chromosome 11p15.4 encodes beta globin, a subunit of adult hemoglobin A, which consists of two alpha and two beta chains. Hundreds of HBB variants cause beta thalassemia, with reduced or absent beta globin production, or structural hemoglobin variants. The sickle cell mutation is a single nucleotide change, GAG to GTG, that replaces glutamic acid with valine at position 6. Under low oxygen, hemoglobin S polymerizes and red blood cells become rigid and sickle shaped. Sickle cell trait protects against severe malaria, which explains its high frequency in sub Saharan Africa and other historically malarial regions. Sickle cell disease causes vaso occlusive crises, hemolytic anemia, splenic infarction, stroke, acute chest syndrome, and priapism. Linus Pauling and colleagues described sickle cell anemia as a molecular disease in 1949. Hydroxyurea increases fetal hemoglobin, reducing sickling. Beta thalassemia major, or Cooley anemia, requires lifelong transfusion support and iron chelation. In 2023 exagamglogene autotemcel, a CRISPR based therapy that reactivates fetal hemoglobin, was approved for sickle cell disease and transfusion dependent beta thalassemia.