Genetics and complement in atypical HUS

Pediatr Nephrol. 2010 Dec;25(12):2431-42. doi: 10.1007/s00467-010-1555-5. Epub 2010 Jun 6.


Central to the pathogenesis of atypical hemolytic uremic syndrome (aHUS) is over-activation of the alternative pathway of complement. Following the initial discovery of mutations in the complement regulatory protein, factor H, mutations have been described in factor I, membrane cofactor protein and thrombomodulin, which also result in decreased complement regulation. Autoantibodies to factor H have also been reported to impair complement regulation in aHUS. More recently, gain of function mutations in the complement components C3 and Factor B have been seen. This review focuses on the genetic causes of aHUS, their functional consequences, and clinical effect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Atypical Hemolytic Uremic Syndrome
  • Autoantibodies / blood
  • Complement Activation / genetics*
  • Complement System Proteins / genetics*
  • Complement System Proteins / immunology
  • Genetic Predisposition to Disease
  • Hemolytic-Uremic Syndrome / genetics
  • Hemolytic-Uremic Syndrome / immunology
  • Humans
  • Mutation*
  • Penetrance
  • Phenotype
  • Risk Assessment
  • Risk Factors


  • Autoantibodies
  • Complement System Proteins