Genetics and genetic testing in hemolytic uremic syndrome/thrombotic thrombocytopenic purpura

The hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are rare diseases that manifest with thrombocytopenia and microangiopathic hemolytic anemia accompanied by renal and neurologic dysfunction. Most childhood cases of HUS are caused by Shiga-toxin-producing bacteria and have a good prognosis. The other form, atypical HUS (aHUS), accounts for 10% of cases. Prognosis of aHUS and TTP has changed over time from fatal disorders to 60% to 80% survival in the plasma therapy era. In the past 10 years the molecular bases of aHUS and TTP have been discovered that mostly lead to uncontrolled activation of the complement system in aHUS and to abnormal von Willebrand factor processing in TTP. Identification of the underlying abnormality in an individual patient can provide prognostically significant information in predicting long-term outcome, response to therapies, and transplant outcome. It also paves the way for the use of specific new therapies in the near future.