Paroxysmal nocturnal hemoglobinuria: An acquired genetic disease

✍ Scribed by Nishimura, Jun-ichi; Murakami, Yoshiko; Kinoshita, Taroh

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 355 KB
• Volume: 62
• Category: Article
• ISSN: 0361-8609
• DOI: 10.1002/(sici)1096-8652(199911)62:3<175::aid-ajh7>3.0.co;2-8

✦ Synopsis

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterized by an intravascular hemolytic anemia. Abnormal blood cells lack a series of glycosylphosphatidylinositol (GPI)-anchored proteins. The lack of GPIanchored complement regulatory proteins, such as decay-accelerating factor (DAF) and CD59, results in complement-mediated hemolysis and hemoglobinuria. In the affected hematopoietic cells from patients with PNH, the first step in biosynthesis of the GPI anchor is defective. At least four genes are involved in this reaction step, and one of them, an X-linked gene termed PIG-A, is mutated in affected cells. The PIG-A gene is mutated in all patients with PNH reported to date. Here, we review recent advances in the understanding of the molecular pathogenesis of PNH.