Paroxysmal nocturnal hemoglobinuria | Aplastic Anemia and MDS International Foundation

Paroxysmal nocturnal hemoglobinuria

Journal Title: 
Blood
Author(s): 
Brodsky RA
Primary Author: 
Brodsky RA
Original Publication Date: 
Thursday, September 18, 2014

Paroxysmal nocturnal hemoblobinuria (PNH) is a rare bone marrow failure disorder that manifests with hemolytic anemia, thrombosis and peripheral blood cytopenias. The absence of two GPI-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for hemolysis and other PNH manifestations. GPI anchor protein deficiency is almost always due to somatic mutations in PIGA, a gene involved in the first step of GPI anchor biosynthesis; however, alternative mutations that cause PNH have recently been discovered. In addition, hypomorphic germline PIGA that do not cause PNH have been shown to be responsible for a condition known as multiple congenital anomalies-hypotonia-seizures syndrome 2. Eculizumab, first-in-class monoclonal antibody that inhibits terminal complement, is the treatment of choice for patients with severe manifestations of PNH. Bone marrow transplantation remains the only cure for PNH but should be reserved for patients with suboptimal response to eculizumab.