Definition of Spherocytosis, hereditary (HS)

Spherocytosis, hereditary (HS): A genetic disorder of the red blood cell membrane clinically characterized by anemia, jaundice (yellowing) and splenomegaly (enlargement of the spleen).

In HS the red cells are smaller, rounder, and more fragile than normal. The red cells have a spherical rather than the biconcave-disk shape of the normal red cell. These rotund red cells (spherocytes) are osmotically fragile and less flexible than normal red cells and tend to get trapped in narrow blood passages, particularly in the spleen, and there they break up (hemolyze) leading to hemolytic anemia.

The clogging of the spleen with red cells almost invariably causes splenomegaly. The breakup of the red cells releases hemoglobin and the heme part gives rise to bilirubin, the pigment of jaundice. The excess bilirubin leads to the formation of gallstones, even in childhood, There is also often iron overload due to the excess destruction of iron-rich red cells.

Hereditary spherocytosis is most common in people of northern European ancestry. It often shows up in infancy or early childhood, causing anemia and jaundice. The bone marrow has to work extra hard to make more red cells. So, if in the course of an ordinary viral illness, the bone marrow stops making red cells, the anemia can quickly become profound. This is termed an aplastic crisis.

Laboratory studies show evidence not only of many spherocytes but also increased numbers of reticulocytes (young red blood cells), hyperbilirubinemia (increased blood levels of the jaundice pigment bilirubin due to the breakup of the red cells) and increased osmotic fragility of the red cells.

HS is due to a deficiency of a protein called ankyrin. Ankyrins are cell membrane proteins (thought to interconnect integral proteins with the spectrin-based membrane skeleton.) The ankyrin of red blood cells (erythrocytic ankyrin) is called ankyrin-R or ankyrin-1. It is represented by the symbol ANK1.

The HS gene, that for ANK1, has been mapped to chromosome 8 and, specifically, to chromosome band 8p11.2. HS is inherited as a dominant trait so, if a person with HS reproduces, their child (irrespective of whether it is a boy or girl) has a 50:50 chance to have HS.

The treatment of hereditary spherocytosis is to remove the spleen (splenectomy). Although the red cell defect persists, the breakup of the red cells (hemolysis) ceases. Splenectomy, however, is a hazard in young children. Young children without a spleen are at increased risk for overwhelming sepsis (bloodstream infection), particularly with the pneumococcus bacteria. Splenectomy is therefore usually postponed if possible until the age of 3 years. Before having a splenectomy, anyone with HS should have the pneumococcal vaccine. Persons with HS (or another cause of brisk ongoing hemolysis) should take supplemental folic acid.

The prognosis (outlook) after splenectomy is for a normal life and a normal life expectancy.

HS is also known as congenital hemolytic jaundice, severe atypical spherocytosis, spherocytosis type II, ankyrin deficiency, erythrocyte ankyrin deficiency, ankyrin-R deficiency, and ankyrin1 deficiency.