Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal haematopoietic stem cell 
(HSC) disease that presents with haemolytic anaemia, thrombosis and smooth 
muscle dystonias, as well as bone marrow failure in some cases. PNH is caused by 
somatic mutations in PIGA (which encodes phosphatidylinositol 
N-acetylglucosaminyltransferase subunit A) in one or more HSC clones. The gene 
product of PIGA is required for the biosynthesis of glycosylphosphatidylinositol 
(GPI) anchors; thus, PIGA mutations lead to a deficiency of GPI-anchored 
proteins, such as complement decay-accelerating factor (also known as CD55) and 
CD59 glycoprotein (CD59), which are both complement inhibitors. Clinical 
manifestations of PNH occur when a HSC clone carrying somatic PIGA mutations 
acquires a growth advantage and differentiates, generating mature blood cells 
that are deficient of GPI-anchored proteins. The loss of CD55 and CD59 renders 
PNH erythrocytes susceptible to intravascular haemolysis, which can lead to 
thrombosis and to much of the morbidity and mortality of PNH. The accumulation 
of anaphylatoxins (such as C5a) from complement activation might also have a 
role. The natural history of PNH is highly variable, ranging from quiescent to 
life-threatening. Therapeutic strategies include terminal complement blockade 
and bone marrow transplantation. Eculizumab, a monoclonal antibody complement 
inhibitor, is highly effective and the only licensed therapy for PNH.