Paroxysmal nocturnal hemoglobinuria (Paroxysmal nocturnal hemoglobinuria) - Gen PIGA.

Paroxysmal nocturnal hemoglobinuria is the alteration resulting in impaired production of erythrocytes, leukocytes and thrombocytes, and leads to premature death. This disease affects both sexes equally and can occur at any age, but is most often diagnosed in adulthood.

Affected individuals manifested paroxysmal symptoms that may be caused by tension in the body, such as infections or recurrent physical effort. During these episodes, hemolysis occurs. Moreover, those affected may exhibit hemoglobinuria that results in a dark urine due to the presence of hemoglobin, the protein that carries oxygen in the blood. In many but not all cases, the hemoglobinuria is most noticeable in the morning.

Premature disintegration of erythrocytes causes hemolytic anemia, which can cause signs and symptoms such as fatigue, weakness, paleness, shortness of breath and increased heart rate. People paroxysmal nocturnal hemoglobinuria with can also be prone to infections due to a deficiency of white blood cells. In addition, abnormal thrombocytes associated with paroxysmal nocturnal hemoglobinuria can cause problems in the process of blood clotting. As a result, affected individuals may have thrombosis, especially in large abdominal veins or, less commonly, bleeding episodes. Individuals with hemoglobinuria paroxysmal nocturnal are at increased risk of developing leukemia. In some cases, people who have been treated for aplastic anemia can develop paroxysmal nocturnal hemoglobinuria.

This process is due to mutations in the gene PIGA, located on the short arm of the X chromosome (Xp22.1). This gene encodes a protein called phosphatidylinositol glycan class A. This protein is involved in a series of processes encoding a molecule called GPI anchor. Specifically, phosphatidylinositol glycan class A is involved in the first step of the sequence encoding an intermediate molecule called phosphatidylinositol N-acetylglucosaminyl or GlcNAc-PI. This step is carried out in the endoplasmic reticulum of the cell. The PIGA protein is a complex with several other proteins and this complex helps initiate the reaction that produces GlcNAc-PI. GPI anchor many different proteins attached to the cell membrane, thus ensuring that these proteins are available when needed on the cell surface.

They have identified more than 100 somatic mutations in the gene PIGA. Some of these mutations alter amino acids in phosphatidylinositol glycan class A, impairing their function. Other mutations lead to the insertion of a premature stop signal encoding phosphatidylinositol glycan class A. As a consequence, an abnormally small protein, which is encoded is usually unstable. In people with paroxysmal noctural hemoglobinuria somatic gene mutations occur in PIGA hematopoietic stem cells, which are primarily found in the bone marrow. These cells produce erythrocytes, leucocytes and thrombocytes. Individuals with hemoglobinuria paroxysmal nocturnal have one or more mutations in the gene PIGA in their hematopoietic stem cells, which leads to the codification of abnormal blood cells. As abnormal hematopoietic stem cells multiply, populations of abnormal blood cells are formed by normal blood cells encoded by the normal hematopoietic stem cells. It is likely that certain abnormal white blood cells initiate an autoimmune process. In addition, abnormal hematopoietic stem cells in people with paroxysmal nocturnal hemoglobinuria may be more susceptible to apoptosis, which causes cells to self - destruct when they are damaged or are not necessary. The proportion of abnormal blood cells in the body affects the severity of signs and symptoms of paroxysmal nocturnal hemoglobinuria, including the risk of thrombosis and hemoglobinuria.

This disease is acquired, rather than be inherited. The disease is due to new mutations in the gene PIGA and generally expressed in people with no history of disease in your family. The disease to children of people affected is not transmitted.

Tests in IVAMI: in IVAMI perform detection of mutations associated with paroxysmal noctural hemoglobinuria by complete PCR amplification of exons PIGA gene, and subsequent sequencing.

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).