Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria, known as PNH, is a rare, acquired, life threatening blood disease in which the immune system destroys red blood cells. Unlike inherited hemolytic conditions, PNH arises from an acquired defect in blood cell membrane proteins rather than an inherited gene passed from a parent. The disease develops when hematopoietic stem cells acquire a mutation in the PIGA gene on the X chromosome, causing red blood cells to lack glycophosphatidylinositol anchors that normally hold protective proteins such as CD55 and CD59 on the cell surface; without these anchors the complement system, part of the body's innate immune defense, attacks red blood cells within the blood vessels, causing intravascular hemolysis. Classic symptoms include red colored urine from broken down hemoglobin, though only a minority of patients notice this; most experience fatigue, shortness of breath and palpitations from anemia. About forty percent of patients develop dangerous blood clots in unusual sites such as the liver veins or brain vessels. PNH occurs in about one to two people per million each year, and untreated disease carries a ten to twenty year prognosis.