What are the genetic changes related to hereditary spherocytosis ?
Mutations in at least five genes cause hereditary spherocytosis. These genes provide instructions for producing proteins that are found on the membranes of red blood cells. These proteins transport molecules into and out of cells, attach to other proteins, and maintain cell structure. Some of these proteins allow for cell flexibility; red blood cells have to be flexible to travel from the large blood vessels (arteries) to the smaller blood vessels (capillaries). The proteins allow the cell to change shape without breaking when passing through narrow capillaries.  Mutations in red blood cell membrane proteins result in an overly rigid, misshapen cell. Instead of a flattened disc shape, these cells are spherical. Dysfunctional membrane proteins interfere with the cell's ability to change shape when traveling through the blood vessels. The misshapen red blood cells, called spherocytes, are removed from circulation and taken to the spleen for destruction. Within the spleen, the red blood cells break down (undergo hemolysis). The shortage of red blood cells in circulation and the abundance of cells in the spleen are responsible for the signs and symptoms of hereditary spherocytosis.  Mutations in the ANK1 gene are responsible for approximately half of all cases of hereditary spherocytosis. The other genes associated with hereditary spherocytosis each account for a smaller percentage of cases of this condition.