title: CFH gene mutation in a case of Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS).
abstract: BACKGROUND
  We report the case of a patient with Shiga toxin (Stx)-associated hemolytic-uremic syndrome (HUS) (STEC-HUS) with a concomitant heterozygous mutation of the gene coding for complement Factor H (CFH).
  
  
  METHODS
  An 18-month-old patient presented with hemolytic anemia and thrombotic microangiopathy in the context of acute gastroenteritis. While the patient did not show kidney or other organ failure, he had persistent hemolysis and complement 3 activation (low C3), leading to the decision to commence immunotherapy with eculizumab (Soliris®) together with transient antibiotic coverage and meningococcal vaccination. Patient outcome was favorable. Diagnostic work-up identified Escherichia coli-associated Type 2 Shiga toxin. Complement analysis showed a heterozygous mutation of the CFH gene (c.2103 G>A, p. Trp701X) resulting in a quantitative CFH defect.
  
  
  CONCLUSIONS
  We report a case of STEC-HUS with a quantitative CFH defect caused by a mutation of the CFH gene. To the best of our knowledge, very few cases of STEC-HUS with complement gene mutation have been reported, but none to date with a CFH mutation. We therefore suggest that complement analyses be performed in patients diagnosed with STEC-HUS in association with low C3 levels, especially in patients presenting with severe or unexpected clinical symptoms.
authors.affiliation: Service de Pédiatrie 1, Centre Hospitalier Universitaire de Strasbourg, Avenue Molière, 67098, Strasbourg Cedex, France. Caroline.caillaud@chru-strasbourg.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Caillaud
authors.affiliation: Service de Pédiatrie 1, Centre Hospitalier Universitaire de Strasbourg, Avenue Molière, 67098, Strasbourg Cedex, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Zaloszyc
authors.affiliation: Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Christoph
authors.initials: C
authors.lastname: Licht
authors.affiliation: Service de Pédiatrie, Centre Hospitalier de Mulhouse, Mulhouse, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Pichault
authors.affiliation: Service d'Immunologie Biologique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.affiliation: Service de Pédiatrie 1, Centre Hospitalier Universitaire de Strasbourg, Avenue Molière, 67098, Strasbourg Cedex, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Fischbach
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003176:Complement C3 / Q000032:analysis; D017242:Complement Factor H / Q000235:genetics; D004252:DNA Mutational Analysis; D004927:Escherichia coli Infections / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology*; D006579:Heterozygote; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D022401:Meningococcal Vaccines / Q000627:therapeutic use; D009154:Mutation; D010641:Phenotype; D012307:Risk Factors; D054323:Shiga-Toxigenic Escherichia coli / Q000472:pathogenicity*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C038245:C3 protein, human; C493495:CFH protein, human; D003176:Complement C3; D005819:Genetic Markers; D007155:Immunologic Factors; D022401:Meningococcal Vaccines; D017242:Complement Factor H; C481642:eculizumab
keywords: CFH gene mutation; Child; Complement; Eculizumab; Shigatoxin; Shigatoxin-associated hemolytic-uremic syndrome