Atypical hemolytic uremic syndrome

A classification of hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP)--the two main variants of thrombotic microangiopathies (TMA)-and related disorders according to etiology has been proposed by the European Pediatric Research Group for HUS [1]. In common medical language, the names typical or post-diarrheal (D+) HUS describe the most frequent form of HUS in children, due to Shiga-toxin (Stx) producing Escherichia coli (STEC), mostly E coli 0157:H7. By opposition, the name atypical HUS (aHUS) has been historically used to describe any HUS not due to STEC, thus including:i) "Secondary" aHUS, due to a variety of causes, including infectious agents different from STEC, mostly Streptococcus pneumoniae (S pneumoniae) (via neuraminidase of S pneumoniae and T antigen exposure), human immunodeficiency virus and H1N1 influenza A, malignancy, cancer chemotherapy and ionizing radiation, bone marrow or solid organ transplantation, calcineurin inhibitors, sirolimus or anti vascular endothelial growth factor (VEGF) agents, pregnancy, HELLP (Hemolytic anemia, elevated Liver enzymes, and Low Platelets) syndrome, malignant hypertension, glomerulopathies, systemic diseases (systemic lupus erythematous and antiphospholipid antibody syndrome, sclerodermia) or, in children, methyl malonic aciduria with homocystinuria, cblC type, a rare hereditary defect of cobalamine metabolism [1-14]. Of note, it is now acknowledged that using the aHUS terminology rather than an etiological-based denomination (e.g. S pneumoniae-HUS) is inadequate [1].ii) aHUS classified as "primary", at least until the years 2000, as no exogenous cause was identified and the mechanism was unknown. However, it was recognized nearly four decades ago that this form of HUS could be familial, touching members of the family several years apart [15]. This is why it is also described as hereditary HUS. During the last decade, this form of aHUS has been demonstrated to be a disease of complement dys