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Membrano-proliferative glomerulonephritis, atypical hemolytic uremic syndrome, and a new complement factor H mutation: report of a case

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Complement protein factor H (CFH) is a regulatory protein of the alternative complement pathway (AP); CFH mutations lead to a spectrum of different phenotypical manifestations of renal disease.


We report the case of a boy with a novel CFH gene mutation who presented with a membranoproliferative (MPGN) pattern of glomerular injury and developed 2 years later atypical hemolytic uremic syndrome (aHUS); this description shows that CFH alteration leads to two different renal diseases in the same patient.


Our case suggests the possibility that complement dysregulation could determine different renal conditions, which may be part of the same disease spectrum. Early recognition of an evolution of glomerulopathies into aHUS may allow appropriate management and prevention of life-threatening consequences.

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  1. Noris M, Remuzzi G (2009) Atypical hemolytic-uremic syndrome. N Engl J Med 361:1676–1687

    Article  PubMed  CAS  Google Scholar 

  2. Pickering M, Cook HT (2011) Complement and glomerular disease: new insights. Curr Opin Nephrol Hypertens 20:271–277

    Article  PubMed  CAS  Google Scholar 

  3. Gale DP, de Jorge EG, Cook HT, Martinez-Barricarte R, Hadjisavvas A, McLean AG, Pusey CD, Pierides A, Kyriacou K, Athanasiou Y, Voskarides K, Deltas C, Palmer A, Frémeaux-Bacchi V, de Cordoba SR, Maxwell PH, Pickering MC (2010) Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. Lancet 376:794–801

    Article  PubMed  CAS  Google Scholar 

  4. Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G (2010) Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 5:1844–1859

    Article  PubMed  CAS  Google Scholar 

  5. Servais A, Noël LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grünfeld JP, Niaudet P, Lesavre P, Frémeaux-Bacchi V (2012) Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int. doi:10.1038/ki.2012.63

  6. Caprioli J, Castelletti F, Bucchioni S, Bettinaglio P, Bresin E, Pianetti G, Gamba S, Brioschi S, Daina E, Remuzzi G, Noris M (2003) Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease. Hum Mol Genet 12:3385

    Article  PubMed  CAS  Google Scholar 

  7. Esparza-Gordillo J, Goicoechea de Jorge E, Buil A, Carreras Berges L, López-Trascasa M, Sánchez-Corral P, Rodríguez de Córdoba S (2005) Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32. Hum Mol Genet 14:703–712

    Article  PubMed  CAS  Google Scholar 

  8. Saunders RE, Goodship TH, Zipfel PF, Perkins SJ (2006) An interactive web database of factor H-associated hemolytic uremic syndrome mutations: insights into the structural consequences of disease-associated mutations. Hum Mutat 27:21–30

    Article  PubMed  CAS  Google Scholar 

  9. Zipfel PF, Mache C, Muller D, Licht C, Wigger M, Skerka C, European DEAP-HUS Study group (2010) DEAP-HUS: deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome. Pediatr Nephrol 25:2009–2019

    Article  PubMed  Google Scholar 

  10. Caprioli J, Bettinaglio P, Zipfel PF, Amadei B, Daina E, Gamba S, Skerka C, Marziliano N, Remuzzi G, Noris M (2001) 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 12:297–307

    PubMed  CAS  Google Scholar 

  11. Licht C, Weyersberg A, Heinen S, Stapenhorst L, Devenge J, Beck B, Waldherr R, Kirschfink M, Zipfel PF, Hoppe B (2005) Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15. Am J Kidney Dis 45:415–421

    Article  PubMed  CAS  Google Scholar 

  12. Appel GB, Cook HT, Hageman G, Jennette JC, Kashgarian M, Kirschfink M, Lambris JD, Lanning L, Lutz HU, Meri S, Rose NR, Salant DJ, Sethi S, Smith RJ, Smover W, Tully HF, Tully SP, Walker P, Welsh M, Wurzner R, Zipfel PF (2005) Membranoproliferative glomerulonephritis type II (dense deposit disease): an update. J Am Soc Nephrol 16:1392–1403

    Article  PubMed  Google Scholar 

  13. Dragon-Durey MA, Frémeaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschennes G, Coppo P, Herman Friedman W, Weiss L (2004) 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 15:787–795

    Article  PubMed  CAS  Google Scholar 

  14. Leroy V, Fremeaux-Bacchi V, Peuchmaur M, Boudouin V, Deschenes G, Macher MA, Loirat C (2010) Membrano proliferative glomerulonephritis with C3NeF and genetic complement dysregulation. Pediatr Nephrol 26:419–424

    Article  PubMed  Google Scholar 

  15. Sethi S, Fervenza C (2012) Membranoproliferative glomerulonephritis. A new look at an old entity. N Engl J Med 366:1119–1131

    Article  PubMed  CAS  Google Scholar 

  16. Skerka C, Licht C, Mengel M, Uzonyi B, Strobel S, Zipfel PF, Zozsi M (2009) Autoimmune forms of thrombotic microangiopathy and membranoproliferative glomerulonephritis: indications for a disease spectrum and common pathogenic principles. Mol Immunol 46:2801–2807

    Article  PubMed  CAS  Google Scholar 

  17. Vaziri-Sani F, Holmberg L, Sjöholm AG, Kristofferson A-C, Manea M, Frémeaux-Bacchi V, Fehrman-Ekholm I, Raafat R, Karpman D (2006) Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome. Kidney Int 69:981–988

    Article  PubMed  CAS  Google Scholar 

  18. Lorcy N, Rioux-Leclercq N, Lombard ML, Le Pogamp P, Vigneau C (2011) Three kidneys, two diseases, one antibody? Nephrol Dial Transplant 26:3811–3813

    Article  PubMed  Google Scholar 

  19. Boyer O, Noël LH, Balzamo E, Guest G, Biebuyck N, Charbit M, Salomon R, Frémeaux-Bacchi V, Niaudet P (2008) Complement factor H deficiency and posttransplantation glomerulonephritis with isolated C3 deposits. Am J Kidney Dis 51:671–677

    Article  PubMed  Google Scholar 

  20. El Karoui K, Hill GS, Karras A, Jacquot C, Moulonguet L, Kourilsky O, Frémeaux-Bacchi V, Delahousse M, Van Huyen JP, Loupy A, Bruneval P, Nochy D (2012) A clinicopathologic study of thrombotic michroangiopathy in IgA nephropathy. J Am Soc Nephrol 23:137–148

    Article  PubMed  CAS  Google Scholar 

  21. Riedl M, Rosales A, Zimmerhackl LB, Jungraithmayr T (2011) Actual and future strategies for transplantation in atypical HUS associated with mutations in factor H. Pediatr Transplant 15:225–228

    Article  PubMed  CAS  Google Scholar 

  22. Waters AM, Licht C (2011) aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol 26:41–57

    Article  PubMed  Google Scholar 

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Correspondence to Lucio Manenti.

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Gnappi, E., Allinovi, M., Vaglio, A. et al. Membrano-proliferative glomerulonephritis, atypical hemolytic uremic syndrome, and a new complement factor H mutation: report of a case. Pediatr Nephrol 27, 1995–1999 (2012).

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