The mutation occurs in one or several hematopoietic stem cell(s) and leads to a lack (total or partial) of all GPI-anchored cell membrane proteins (the most important being CD55 and CD59, involved in the regulation of hemolysis due to complement). PNH is caused by somatic mutations in the PIGA gene (Xp22.1), encoding a protein involved in the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor. Bone marrow failure may occur prior, along, or as a late complication of the disease (40-50 % of cases). PNH is a chronic disease with hemolytic crises that may be triggered by several factors such as common infection, vaccination, surgery or certain antibiotics. Depending on their localization, thromboses (which affect 30-40 % of untreated patients) may manifest as abdominal pain, hepatomegaly, ascites and headaches. Hemoglobinuria results in the production of classically dark urine during the night and in the morning (about 25 % of patients), and patients may present with renal insufficiency. Pallor, fatigue and stress dyspnea with activity are the usual manifestations. The variable clinical manifestations include hemolytic anemia, medium and large vessel thrombosis (mainly involving the hepatic, abdominal, cerebral, and dermal veins), and moderate to severe hematopoietic deficiency that may lead to pancytopenia. The disease may occur at any age but it preferentially affects young adults. Higher frequency is suggested in Southeast Asia and in the Far East. An incidence estimate of about 1/770,000/year has been reported with a predicted prevalence of approximately 1/62,500 in Great Britain. Although PNH has been described worldwide, exact prevalence data are not available.
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