Hereditary spherocytosis

Hereditary spherocytosis is an abnormality of red blood cells, or erythrocytes. The disorder is caused by mutations in genes relating to membrane proteins that allow for the erythrocytes to change shape. The abnormal erythrocytes are sphere-shaped (spherocytosis) rather than the normal biconcave disk shaped. Dysfunctional membrane proteins interfere with the cell's ability to be flexible to travel from the arteries to the smaller capillaries. This difference in shape also makes the red blood cells more prone to rupture. Cells with these dysfunctional proteins are degraded in the spleen. This shortage of erythrocytes results in hemolytic anemia.Ankyrin: Long QT syndrome 4 Hereditary spherocytosis is an abnormality of red blood cells, or erythrocytes. The disorder is caused by mutations in genes relating to membrane proteins that allow for the erythrocytes to change shape. The abnormal erythrocytes are sphere-shaped (spherocytosis) rather than the normal biconcave disk shaped. Dysfunctional membrane proteins interfere with the cell's ability to be flexible to travel from the arteries to the smaller capillaries. This difference in shape also makes the red blood cells more prone to rupture. Cells with these dysfunctional proteins are degraded in the spleen. This shortage of erythrocytes results in hemolytic anemia. It was first described in 1871. It is the most common cause of inherited hemolysis in European and North American Caucasian populations, with an incidence of 1 in 5000 births. The clinical severity of HS varies from symptom-freecarrier to severe hemolysis because the disorder exhibits incomplete penetrance in its expression. Symptoms include anemia, jaundice, splenomegaly, and fatigue. Furthermore, the detritus of the broken-down blood cells – unconjugated or indirect bilirubin – accumulates in the gallbladder, and can cause pigmented gallstones to develop. In chronic patients, an infection or other illness can cause an increase in the destruction of red blood cells, resulting in the appearance of acute symptoms, a hemolytic crisis. On a blood smear, Howell-Jolly bodies may be seen within red blood cells. Primary treatment for patients with symptomatic HS has been total splenectomy, which eliminates the hemolytic process, allowing normal hemoglobin, reticulocyte and bilirubin levels. Acute cases can threaten to cause hypoxia through anemia and acute kernicterus through high blood levels of bilirubin, particularly in newborns. Most cases can be detected soon after birth. An adult with this disease should have their children tested, although the presence of the disease in children is usually noticed soon after birth. Occasionally, the disease will go unnoticed until the child is about 4 or 5 years of age. A person may also be a carrier of the disease and show no signs or symptoms of the disease. Other symptoms may include abdominal pain that could lead to the removal of the spleen and/or gallbladder. Spherocytosis patients who are heterozygous for a hemochromatosis gene may suffer from iron overload, despite the hemochromatosis genes being recessive. Hereditary spherocytosis can be an autosomal recessive or autosomal dominant trait. Hereditary spherocytosis is most commonly (though not exclusively) found in Northern European and Japanese families, although an estimated 25% of cases are due to spontaneous mutations. A patient has a 50% chance of passing the mutation onto each of his/her offspring. Hereditary spherocytosis is caused by a variety of molecular defects in the genes that code for the red blood cell proteins spectrin (alpha and beta), ankyrin, band 3 protein, protein 4.2, and other red blood cell membrane proteins: These proteins are necessary to maintain the normal shape of a red blood cell, which is a biconcave disk. The integrating protein that is most commonly defective is spectrin which is responsible for incorporation and binding of spectrin, thus in its dysfunction cytoskeletal instabilities ensue.