Paroxysmal nocturnal hemoglobinuria as a molecular disease.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, clonal disorder of hematopoietic cells caused by somatic mutation in the X-linked PIGA gene encoding a protein involved in the synthesis of the glycosylphosphatidylinositol (GPI) anchor by which many proteins are attached to the membrane of cells. About 15 proteins have been found to be lacking or markedly deficient on the abnormal blood cells. These defects result in a clinical syndrome that includes intravascular hemolysis mediated by complement, unusual venous thromboses, deficits of hematopoiesis, and other manifestations. Therapy is presently directed mainly at the consequences of the disorder rather than its basic causes and includes replacement of iron, folic acid, and whole blood; hormonal modulation (prednisone, androgens); anticoagulation; and bone marrow transplantation. PNH is a chronic disease with more than half of adult patients surviving 15 years or more; prognosis is less good in children.