Hereditary spherocytosis (Hereditary spherocytosis) - Genes ANK1, EPB42, SLC4A1, SPTA1 and SPTB.
Hereditary spherocytosis is a disorder that affects red blood cells. People with this disease often have anemia, jaundice and splenomegaly. Most infants with hereditary spherocytosis have severe anemia, although improvement after the first year of life. Splenomegaly can appear at any time from early childhood to adulthood. In addition, about half of affected individuals develop gallstones, which usually occur from late childhood to middle adulthood.
They described four forms of hereditary spherocytosis, which differ in the severity of the signs and symptoms. They are known as mild, the moderate, moderate / severe form, and the severe form. It is estimated that between 20% and 30% of people with hereditary spherocytosis have mild, between 60% and 70% are moderately, 10% had moderate / severe form, and from 3% and 5% of those affected by hereditary spherocytosis have the severe form.
People with mild anemia can be mild or sometimes no symptoms. People with moderately often have anemia, jaundice and splenomegaly. In addition, many also develop gallstones. Usually the signs and symptoms of moderate hereditary spherocytosis appear in childhood. For its part, individuals with moderate / severe form have all the features of moderate, but they also have severe anemia. Those with the severe form, have life - threatening anemia that requires regular blood transfusions to replenish their supply of red blood cells. They also have severe splenomegaly, jaundice and a high risk of developing gallstones. Some people with the severe form have short stature, delayed sexual development and skeletal abnormalities.
Hereditary spherocytosis is due to mutations in genes ANK1, located on the short arm of chromosome 8 (8p11.1), EPB42, located on the long arm of chromosome 15 (15q15-q21), SLC4A1, located on the long arm of chromosome 17 (17q21.31), SPTA1, located on the long arm of chromosome 1 (1q21) and SPTB, located on the long arm of chromosome 14 (14q23-q24.2). These genes encode proteins found on the membranes of erythrocytes. Some of these proteins allow flexibility of the required cell to circulate the arteries to the capillaries. These proteins allow the cell to change shape as it passes through the narrow capillaries.
Mutations in these genes lead to an excessively rigid and deformed cell. Instead of a flattened disk shape, these cells are spherical. Dysfunctional proteins interfere with the ability of the cell to change shape when flowing through blood vessels. Misshapen red blood cells, called spherocytes are withdrawn from circulation and taken to the spleen to undergo hemolysis. Deficiency of erythrocytes in circulation and the abundance of cells in the spleen are responsible for the signs and symptoms of hereditary spherocytosis. Mutations in the gene ANK1 are responsible for about half of all cases of hereditary spherocytosis. Each of the other genes associated with hereditary spherocytosis represent a smaller percentage of cases occur.
In approximately 75% of cases, hereditary spherocytosis is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. In some cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family. This disease can also be inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with hereditary spherocytosis, by complete PCR amplification of the exons of ANK1, EPB42, SLC4A1, SPTA1 and SPTB, respectively, and subsequent sequencing genes.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).