title: Molecular Pathogenesis of Paroxysmal Nocturnal Hemoglobinuria.
abstract: Paroxysmal nocturnal hemoglobinuria (PNH), although named for its marked fluctuations in the visibility of hemoglobinuria, is now classified as an acquired hematopoietic stem cell disorder. The clinical manifestations of PNH are very complicated, and include intravascular hemolytic anemia, venous thrombosis in unusual sites (abdomen, liver, cerebrum), deficient hematopoiesis, evolution to leukemia, and susceptibility to infection [1, 2]. The intravascular hemolysis is attributed to the enhanced susceptibility of erythrocytes to autologous complement [3]. The abnormal sensitivity is explained by a lack of complement regulatory membrane proteins such as decay-accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), which are covalently linked to the erythrocyte membrane through a glycosylphosphatidylinositol (GPI) anchor. The deficiency of the membrane proteins is caused by a synthetic defect in this anchor caused by impaired transfer of N- acetylglucosamine (GlcNAc) to phosphatidylinositol (PIns) [2]. Mutations of the phosphatidylinositol glycan class A (PIG-A) gene have been shown to contribute this abnormality in nearly all patients with PNH studied to date [4]. Recently, several reviews have been presented on various aspects of PNH [5-10]. This review focuses particularly on the recent elucidation of the molecular pathogenesis of GPI-anchor deficiency on PNH and related hematopoietic stem cell disorders.
authors.affiliation: a Institute of Biochemistry, School of Medical Technology , Department of Laboratory Medicine , College of Medicine, National Taiwan University.
authors.forename: L I
authors.initials: LI
authors.lastname: Lin
authors.affiliation: a Institute of Biochemistry, School of Medical Technology , Department of Laboratory Medicine , College of Medicine, National Taiwan University.
authors.forename: Y C
authors.initials: YC
authors.lastname: Chen
authors.affiliation: a Institute of Biochemistry, School of Medical Technology , Department of Laboratory Medicine , College of Medicine, National Taiwan University.
authors.forename: J K
authors.initials: JK
authors.lastname: Lin
keywords: PIG-A gene; Paroxysmal nocturnal hemoglobinuria (PNH); glycosylphosphatidylinositol (GPI)