title: Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics.
abstract: BACKGROUND
  Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (αFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (∆CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS).
  
  
  METHODS
  Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome.
  
  
  RESULTS
  In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xαFH, of which five had ∆CFHR1/3); four patients carried combined genetic defects or a mutation, together with αFH. In the majority (87%), disease onset was preceeded by a triggering event; in 25% of cases diarrhea was the presenting symptom. More than 50% had normal serum C3 levels at presentation. Relapses were seen in half of the patients, and there was renal graft failure in all except one case following transplant.
  
  
  CONCLUSIONS
  Performing adequate DNA analysis is essential for treatment and positive outcome in children with aHUS. The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options.
authors.affiliation: Department of Pediatric Nephrology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. lgeerdink@gmail.com
authors.forename: Lianne M
authors.initials: LM
authors.lastname: Geerdink
authors.forename: Dineke
authors.initials: D
authors.lastname: Westra
authors.forename: Joanna A E
authors.initials: JA
authors.lastname: van Wijk
authors.forename: Eiske M
authors.initials: EM
authors.lastname: Dorresteijn
authors.forename: Marc R
authors.initials: MR
authors.lastname: Lilien
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Davin
authors.forename: Martin
authors.initials: M
authors.lastname: Kömhoff
authors.forename: Koen
authors.initials: K
authors.lastname: Van Hoeck
authors.forename: Amerins
authors.initials: A
authors.lastname: van der Vlugt
authors.forename: Lambertus P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: Nicole C A J
authors.initials: NC
authors.lastname: van de Kar
mesh_terms: D017668:Age of Onset; D065766:Atypical Hemolytic Uremic Syndrome; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003165:Complement System Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D003165:Complement System Proteins