Clinical and Experimental Nephrology

, Volume 13, Issue 5, pp 526–530 | Cite as

Hemolytic uremic syndrome due to homozygous factor H deficiency

  • Sidharth Kumar Sethi
  • Dragon-Durey Marie-Agnes
  • Neelam Thaker
  • Pankaj Hari
  • Arvind Bagga
Case Report


The majority of complement factor H mutations associated with atypical hemolytic uremic syndrome (HUS) are heterozygous. Homozygous mutations causing atypical hemolytic uremic syndrome are rare. We report a 7-month-old boy with HUS, severe hypocomplementemia (low C3 and normal C4 levels), and extremely low circulating levels of factor H. Genetic analysis showed homozygous 4 bp deletion in the gene encoding factor H in the patient, with his parents being carriers. The patient showed progression to end-stage renal disease and is presently on chronic ambulatory peritoneal dialysis.


Factor H Hemolytic uremic syndrome Homozygous factor H deficiency Thrombotic microangiopathy 



We thank Jacques Blouin, Nelly Poulain, and Christine Hautreux for their technical assistance.


  1. 1.
    Taylor CM. Complement factor H and the haemolytic uraemic syndrome. Lancet. 2001;358:1200–2.CrossRefPubMedGoogle Scholar
  2. 2.
    Noris M, Ruggenenti P, Perna A, Orisio S, Caprioli J, Skerka C, et al. Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura. J Am Soc Nephrol. 1999;10:281–93.PubMedGoogle Scholar
  3. 3.
    Caprioli J, Noris M, Brioschi S, Pianetti G, Castelletti F, Bettinaglio P, et al. International Registry of Recurrent and Familial HUS/TTP; Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267–79.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Dragon-Durey MA, Frémeaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschenes G, et al. Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases. J Am Soc Nephrol. 2004;15:787–95.CrossRefPubMedGoogle Scholar
  5. 5.
    Pichette V, Quérin S, Schürch W, Brun G, Lehner-Netsch G, Delâge J. Familial hemolytic–uremic syndrome and homozygous factor H deficiency. Am J Kidney Dis. 1994;24:936–41.CrossRefPubMedGoogle Scholar
  6. 6.
    Ohali M, Shalev H, Schlesinger M, Katz Y, Kachko L, Carmi R, et al. Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H. Pediat Nephrol. 1998;12:619–24.CrossRefPubMedGoogle Scholar
  7. 7.
    Kazatchkine MD, Hauptmann G, Nydegger U: Techniques de Complément, Paris, Société Française d’Immunologie 1985.Google Scholar
  8. 8.
    Kazatchkine MD, Fearon DT, Austen KF. Human alternative complement pathway: membrane-associated sialic acid regulates the competition between B and β1 H for cell-bound C3b. J Immunol. 1979;122:75–81.PubMedGoogle Scholar
  9. 9.
    Jeanpierre M. A rapid method for the purification of DNA from blood. Nucleic Acids Res. 1987;15:9611.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Vaziri-Sani F, Holmberg L, Sjöholm AG, Kristoffersson AC, Manea M, Frémeaux-Bacchi V, et al. Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome. Kidney Int. 2006;69:981–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, Macher MA, Niaudet P, Guest G, et al. French Society of Pediatric Nephrology; differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2007;18:2392–400.CrossRefPubMedGoogle Scholar
  12. 12.
    Schmidt BZ, Fowler NL, Hidvegi T, Perlmutter DH, Colten HR. Disruption of disulfide bonds is responsible for impaired secretion in human complement factor H deficiency. J Biol Chem. 1999;274:11782–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Ault BH, Schmidt BZ, Fowler NL, Kashtan CE, Ahmed AE, Vogt BA, et al. Human factor H deficiency. Mutations in framework cysteine residues and block in H protein secretion and intracellular catabolism. J Biol Chem. 1997;272:25168–75.CrossRefPubMedGoogle Scholar
  14. 14.
    Edey MM, Mead PA, Saunders RE, Strain L, Perkins SJ, Goodship TH, et al. Association of a factor H mutation with hemolytic uremic syndrome following a diarrheal illness. Am J Kidney Dis. 2008;51:487–90.CrossRefPubMedGoogle Scholar
  15. 15.
    Allford SL, Hunt BJ, Rose P, Machin SJ. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol. 2003;120:556–73.CrossRefPubMedGoogle Scholar
  16. 16.
    Saland JM, Emre SH, Shneider BL, Benchimol C, Ames S, Bromberg JS, et al. Favorable long-term outcome after liver–kidney transplant for recurrent hemolytic uremic syndrome associated with a factor H mutation. Am J Transplant. 2006;6:1948–52.CrossRefPubMedGoogle Scholar
  17. 17.
    Jalanko H, Peltonen S, Koskinen A, Puntila J, Isoniemi H, Holmberg C, et al. Successful liver–kidney transplantation in two children with aHUS caused by a mutation in complement factor H. Am J Transplant. 2008;8:216–21.PubMedGoogle Scholar
  18. 18.
    Thompson RA, Winterborn MH. Hypocomplementaemia due to a genetic deficiency of beta 1H globulin. Clin Exp Immunol. 1981;46:110–9.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Landau D, Shalev H, Levy-Finer G, Polonsky A, Segev Y, Katchko L. Familial hemolytic uremic syndrome associated with complement factor H deficiency. J Pediatr. 2001;138:412–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Caprioli J, Bettinaglio P, Zipfel PF, Amadei B, Daina E, Gamba S, et al. Italian Registry of Familial and Recurrent HUS/TTP; The molecular basis of familial hemolytic uremic syndrome: mutation analysis of factor H gene reveals a hot spot in short consensus repeat 20. J Am Soc Nephrol. 2001;12:297–307.PubMedGoogle Scholar
  21. 21.
    Cho HY, Lee BS, Moon KC, Ha IS, Cheong HI, Choi Y. Complete factor H deficiency-associated atypical hemolytic uremic syndrome in a neonate. Pediatr Nephrol. 2007;22:874–80.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2009

Authors and Affiliations

  • Sidharth Kumar Sethi
    • 1
  • Dragon-Durey Marie-Agnes
    • 2
  • Neelam Thaker
    • 1
  • Pankaj Hari
    • 1
  • Arvind Bagga
    • 1
  1. 1.Division of Pediatric Nephrology, Department of PediatricsAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Laboratoire d’Immunologie, Hôpital Européen Georges PompidouUniversité Paris DescartesParisFrance

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