What is the cause of hereditary spherocytosis (HS)?

By William Aird

Autosomal dominant (75% of cases) or autosomal recessive (25%) mutations in genes that encode red blood cell (RBC) membrane proteins, resulting in qualitative defects of the encoded proteins. Genes with mutations include:

  • ANK1 encoding ankyrin
  • SLC4A1 encoding band 3
  • SPTA1 encoding alpha-spectrin
  • SPTB encoding beta-spectrin
  • EPB42 encoding protein 4.2

Mutations results in reduced binding of spectrin cytoskeleton to lipid bilayer of RBCs, leading to reduced membrane surface area (reduced surface area-to-volume ratio), reduced RBC deformability and increased osmotic fragility.