title: Mutations in proteins of the alternative pathway of complement and the pathogenesis of atypical hemolytic uremic syndrome.
abstract: Atypical hemolytic uremic syndrome is associated with mutations in the complement proteins factor H, factor I, factor B, C3, or membrane cofactor protein in about 50% of patients. The evolution and prognosis of the disease in patients carrying mutations in factor H is particularly poor, and renal transplantation most often fails because of recurrence of the disease in the graft. The risk of rapid loss of renal function in patients with functional mutations in factor H requires that effective treatment be initiated as soon as possible, but identification of these patients relies on genetic studies that are time consuming. We describe a case in which an in vitro hemolytic assay proved useful for rapidly assessing factor H dysfunction and for testing whether this dysfunction could be corrected with fresh frozen plasma. In the context of this case, we summarize recent advances in understanding the molecular mechanisms contributing to atypical hemolytic uremic syndrome, including descriptions of DNA- and protein-based analysis. We conclude that functional analysis of factor H should help rationalize the plasma treatment of patients with atypical hemolytic uremic syndrome.
authors.affiliation: Research Unit, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Abarrategui-Garrido
authors.forename: Marta
authors.initials: M
authors.lastname: Melgosa
authors.forename: Antonia
authors.initials: A
authors.lastname: Peña-Carrión
authors.forename: Elena Goicoechea
authors.initials: EG
authors.lastname: de Jorge
authors.forename: Santiago Rodríguez
authors.initials: SR
authors.lastname: de Córdoba
authors.forename: Margarita
authors.initials: M
authors.lastname: López-Trascasa
authors.forename: Pilar
authors.initials: P
authors.lastname: Sánchez-Corral
mesh_terms: D003167:Complement Activation; D017242:Complement Factor H / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007223:Infant; D009154:Mutation; D010956:Plasmapheresis; D006435:Renal Dialysis / Q000379:methods; D012131:Respiratory Insufficiency; D012720:Severity of Illness Index
chemical_list: D017242:Complement Factor H