Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder 
that manifests with hemolytic anemia, thrombosis, and peripheral blood 
cytopenias. The absence of two glycosylphosphatidylinositol (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 phosphatidylinositol 
glycan class A (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 germ-line PIGA mutations that do not cause 
PNH have been shown to be responsible for a condition known as multiple 
congenital anomalies-hypotonia-seizures syndrome 2. Eculizumab, a 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.