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Which are the causes of Paroxysmal nocturnal hemoglobinuria?

See some of the causes of Paroxysmal nocturnal hemoglobinuria according to people who have experience in Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria causes

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder characterized by the abnormal breakdown of red blood cells (hemolysis), leading to a range of symptoms including anemia, fatigue, and blood clots. PNH is caused by a mutation in the PIGA gene, which is responsible for producing a protein necessary for the attachment of certain proteins to the cell surface. This mutation results in the deficiency of these proteins, leading to the characteristic features of PNH.



1. PIGA gene mutation: The primary cause of PNH is a mutation in the PIGA gene, which is located on the X chromosome. This mutation occurs in a hematopoietic stem cell, which gives rise to all blood cells. The PIGA gene is responsible for producing an enzyme called phosphatidylinositol glycan class A (PIG-A), which is involved in the production of glycosylphosphatidylinositol (GPI) anchors. GPI anchors attach certain proteins to the cell membrane, including complement regulatory proteins such as CD55 and CD59. The mutation in the PIGA gene leads to a deficiency of these GPI-anchored proteins on the surface of blood cells, making them susceptible to complement-mediated destruction.



2. Complement system dysregulation: The complement system is a part of the immune system that helps in the recognition and elimination of foreign pathogens. In PNH, the deficiency of GPI-anchored proteins on the surface of blood cells leads to the dysregulation of the complement system. Normally, these proteins protect the cells from complement-mediated attack by inhibiting the formation of the membrane attack complex (MAC), which can cause cell lysis. In PNH, the absence of these proteins results in uncontrolled complement activation, leading to the destruction of red blood cells, white blood cells, and platelets.



3. Clonal expansion: Once a hematopoietic stem cell acquires the PIGA gene mutation, it has a growth advantage over normal stem cells. This leads to clonal expansion, where the mutated stem cell gives rise to a population of abnormal blood cells. These abnormal cells lack GPI-anchored proteins and are susceptible to complement-mediated destruction. The clonal expansion of these abnormal cells is responsible for the characteristic features of PNH.



4. Somatic mutations: In some cases, PNH can arise due to somatic mutations in the PIGA gene. Somatic mutations occur after fertilization and are not inherited from parents. These mutations can occur in any cell of the body and are not present in the germline. Somatic mutations in the PIGA gene can lead to the development of PNH in a subset of individuals.



5. Risk factors: While the exact cause of PNH is not fully understood, certain risk factors have been identified. These include certain genetic predispositions, such as a family history of PNH or other bone marrow disorders. Additionally, certain medical conditions, such as aplastic anemia and other bone marrow failure syndromes, have been associated with an increased risk of developing PNH.



In conclusion, Paroxysmal nocturnal hemoglobinuria (PNH) is primarily caused by a mutation in the PIGA gene, leading to a deficiency of GPI-anchored proteins on the surface of blood cells. This deficiency results in complement-mediated destruction of red blood cells, white blood cells, and platelets. Clonal expansion of the mutated cells and somatic mutations in the PIGA gene can contribute to the development of PNH. While the exact cause of PNH is not fully understood, certain genetic predispositions and medical conditions have been identified as risk factors for the development of this rare disorder.


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PAROXYSMAL NOCTURNAL HEMOGLOBINURIA STORIES
Paroxysmal nocturnal hemoglobinuria stories
10 years old girl suffering from PNH
Paroxysmal nocturnal hemoglobinuria stories
_I was diagnosed with Psoriatic arthritis at age 19. After many medication I was put on enbre ant tbf medication. This worked great for 3 years until my platelets and HB started dropping. _ _I was referred to see a haematologist and after 2 years, ...

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