title: A missense mutation in factor I (IF) predisposes to atypical haemolytic uraemic syndrome.
abstract: A genetic predisposition involving complement regulatory genes has become evident in some patients with atypical HUS. In this paper, a patient with a heterozygous missense mutation in factor I (IF) is described. Although the serum level of IF was normal, a mild functional defect in the alternative pathway of complement could be demonstrated in the affected members of the family. After an episode of atypical HUS, chronic renal insufficiency started at the age of 15 months. Recurrence of HUS, with loss of the renal transplant, occurred twice in this patient. The recurrence of HUS in the graft was not reflected by haematological abnormalities (haemolysis, thrombocytopenia). One additional transplant was lost due to arterial thrombosis of the renal artery. This report confirms the gloomy outcome of renal transplants in patients with an IF deficiency. New therapies should be evaluated in these patients.
authors.affiliation: Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. j.geelen@cukz.umcn.nl
authors.forename: Joyce
authors.initials: J
authors.lastname: Geelen
authors.forename: Koen
authors.initials: K
authors.lastname: van den Dries
authors.forename: Anja
authors.initials: A
authors.lastname: Roos
authors.forename: Nicole
authors.initials: N
authors.lastname: van de Kar
authors.forename: Corrie
authors.initials: C
authors.lastname: de Kat Angelino
authors.forename: Ina
authors.initials: I
authors.lastname: Klasen
authors.forename: Leo
authors.initials: L
authors.lastname: Monnens
authors.forename: Lambertus
authors.initials: L
authors.lastname: van den Heuvel
mesh_terms: D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D017244:Complement Factor I / Q000235:genetics*; D003170:Complement Pathway, Alternative; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics* / Q000601:surgery; D006579:Heterozygote; D006801:Humans; D007223:Infant; D016030:Kidney Transplantation; D008297:Male; D020125:Mutation, Missense; D012008:Recurrence; D012086:Reoperation
chemical_list: D003176:Complement C3; D003181:Complement C4; D017244:Complement Factor I