The molecular basis of paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a he. matopoietic stem cell disorder characterized by chronic hemolysis, hemoglobinuria, hemosiderinuria, and a tendency to develop thromboembolic disease. In this disorder blood cells lack membrane proteins that are normally anchored by a phospholipid anchor. Some of these proteins, particularly CD59, are inhibitors of complement mediated lysis; in their absence intravascular destruction of red cells occurs. The basic abnormality is a deficiency in the PIG-A gene, a sex-linked gene that encodes one of the enzymes required for the first step of anchor synthesis, the addition of N-acetylglucosamine to the 6-hydroxyl group of inositol. Treatment of PNH is unsatisfactory. It can be cured by allogeneic stem cell transplantation.