Pediatric Nephrology

, Volume 25, Issue 12, pp 2431–2442

Genetics and complement in atypical HUS

Authors

    • The Institute of Human GeneticsNewcastle University
    • Institute of Human GeneticsInternational Centre for Life
  • Tim Goodship
    • The Institute of Human GeneticsNewcastle University
Educational Review

DOI: 10.1007/s00467-010-1555-5

Cite this article as:
Kavanagh, D. & Goodship, T. Pediatr Nephrol (2010) 25: 2431. doi:10.1007/s00467-010-1555-5

Abstract

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.

Keywords

Hemolytic uremic syndrome Transplantation Complement Factor H Factor I Membrane cofactor protein Thrombomodulin Thrombotic thrombocytopenic purpura

Abbreviations

HUS

Hemolytic uremic syndrome

D+ve HUS

Diarrhoeal-associated hemolytic uremic syndrome

aHUS

Atypical hemolytic uremic syndrome

AP

Alternative pathway

CP

Classical pathway

CCPs

Complement control protein modules

RCA

Regulators of complement activation

ESRF

End-stage renal failure

SNPs

Single nucleotide polymorphisms

Copyright information

© IPNA 2010