title: Association of a factor H mutation with hemolytic uremic syndrome following a diarrheal illness.
abstract: Hemolytic uremic syndrome (HUS) takes 2 forms: diarrheal HUS and nondiarrheal HUS. As its name suggests, diarrheal HUS classically follows an enteric infection. The classic infective organism is the Escherichia coli O157 serotype, although other bacteria, including Shigella species, can produce the verocytotoxin required to cause HUS. The usual clinical course is an episode of bloody diarrhea followed by thrombotic microangiopathy and acute renal failure. Supportive treatment sees recovery of renal function in the vast majority of patients. Most cases occur in children, but all age groups can be affected. Conversely, nondiarrheal HUS may have one of a number of predisposing factors, including drugs, irradiation, and hypertension. It also is well established that mutations in the genes encoding the complement regulator proteins factor H, factor I, and membrane cofactor protein predispose to nondiarrheal HUS. In patients with nondiarrheal HUS, recovery of renal function is much less common. Here, we present a case of HUS after a diarrheal illness in which the patient did not recover renal function in the long term. A novel mutation in exon 23 of the factor H gene was discovered. This is clinically important. If this patient underwent transplantation, he would be expected to have an 80% risk of graft loss at 2 years because of recurrent HUS. We recommend consideration of complement gene mutations in any patient with HUS after a diarrheal episode in which there are unusual features.
authors.affiliation: Department of Nephrology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. mattedey@doctors.org.uk
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Edey
authors.forename: Paul A
authors.initials: PA
authors.lastname: Mead
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Saunders
authors.forename: Lisa
authors.initials: L
authors.lastname: Strain
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Perkins
authors.forename: Timothy H J
authors.initials: TH
authors.lastname: Goodship
authors.forename: N Suren
authors.initials: NS
authors.lastname: Kanagasundaram
mesh_terms: D000328:Adult; D001483:Base Sequence; D017242:Complement Factor H / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D003967:Diarrhea / Q000150:complications; D018450:Disease Progression; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D017242:Complement Factor H; D003404:Creatinine