title: Atypical hemolytic uremic syndrome, genetic basis, and clinical manifestations.
abstract: Atypical hemolytic uremic syndrome (aHUS) is now well recognized to be a disease characterized by excessive complement activation in the microvasculature. In both the familial and sporadic forms, inherited and acquired abnormalities affecting components of the alternative complement pathway are found in ~ 60% of patients. These include mutations in the genes encoding both complement regulators (factor H, factor I, membrane cofactor protein, and thrombomodulin) and activators (factors B and C3) and autoantibodies against factor H. Multiple hits are necessary for the disease to manifest, including a trigger, mutations, and at-risk haplotypes in complement genes. The prognosis for aHUS is poor, with most patients developing end-stage renal failure. Renal transplantation in most patients also has a poor prognosis, with frequent loss of the allograft to recurrent disease. However, improving results with combined liver-kidney transplantation and the advent of complement inhibitors such as eculizumab offer hope that the prognosis for aHUS will improve in future years.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Kavanagh
authors.forename: Timothy H J
authors.initials: TH
authors.lastname: Goodship
mesh_terms: D065766:Atypical Hemolytic Uremic Syndrome; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D051916:Membrane Cofactor Protein / Q000378:metabolism; D012307:Risk Factors
chemical_list: D051916:Membrane Cofactor Protein