Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics

Lianne M. Geerdink*, Dineke Westra, Joanna A. E. van Wijk, Eiske M. Dorresteijn, Marc R. Lilien, Jean-Claude Davin, Martin Komhoff, Koen Van Hoeck, Amerins van der Vlugt, Lambertus P. van den Heuvel, Nicole C. A. J. van de Kar

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

110 Citations (Scopus)

Abstract

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 (alpha FH) with or without a homozygous deletion in CFH-related protein 1 and 3 (a dagger CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS).

Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome.

In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6x alpha FH, of which five had a dagger CFHR1/3); four patients carried combined genetic defects or a mutation, together with alpha FH. 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.

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.

Original languageEnglish
Pages (from-to)1283-1291
Number of pages9
JournalPediatric Nephrology
Volume27
Issue number8
DOIs
Publication statusPublished - Aug-2012

Keywords

  • Atypical HUS
  • Complement regulation
  • Plasma therapy
  • Dialysis
  • Transplantation
  • Clinical outcome
  • FACTOR-H-AUTOANTIBODIES
  • COFACTOR PROTEIN CD46
  • OF-FUNCTION MUTATIONS
  • THROMBOTIC MICROANGIOPATHY
  • FACTOR-B
  • FACTOR-I
  • PREDISPOSE
  • IMPACT
  • TRANSPLANTATION
  • DEFICIENCY

Cite this