Skip to main content
Erschienen in: Pediatric Nephrology 10/2012

01.10.2012 | Brief Report

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

verfasst von: Elisa Gnappi, Marco Allinovi, Augusto Vaglio, Elena Bresin, Annalisa Sorosina, Francesco P. Pilato, Landino Allegri, Lucio Manenti

Erschienen in: Pediatric Nephrology | Ausgabe 10/2012

Einloggen, um Zugang zu erhalten

Abstract

Background

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.

Case-Diagnosis/Treatment

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.

Conclusions

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.
Literatur
1.
2.
Zurück zum Zitat Pickering M, Cook HT (2011) Complement and glomerular disease: new insights. Curr Opin Nephrol Hypertens 20:271–277PubMedCrossRef Pickering M, Cook HT (2011) Complement and glomerular disease: new insights. Curr Opin Nephrol Hypertens 20:271–277PubMedCrossRef
3.
Zurück zum Zitat 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 376:794–801PubMedCrossRef 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 376:794–801PubMedCrossRef
4.
Zurück zum Zitat 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 5:1844–1859PubMedCrossRef 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 5:1844–1859PubMedCrossRef
5.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 12:3385PubMedCrossRef 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 12:3385PubMedCrossRef
7.
Zurück zum Zitat 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 14:703–712PubMedCrossRef 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 14:703–712PubMedCrossRef
8.
Zurück zum Zitat 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 27:21–30PubMedCrossRef 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 27:21–30PubMedCrossRef
9.
Zurück zum Zitat 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 25:2009–2019PubMedCrossRef 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 25:2009–2019PubMedCrossRef
10.
Zurück zum Zitat 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 12:297–307PubMed 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 12:297–307PubMed
11.
Zurück zum Zitat 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 45:415–421PubMedCrossRef 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 45:415–421PubMedCrossRef
12.
Zurück zum Zitat 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 16:1392–1403PubMedCrossRef 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 16:1392–1403PubMedCrossRef
13.
Zurück zum Zitat 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 15:787–795PubMedCrossRef 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 15:787–795PubMedCrossRef
14.
Zurück zum Zitat 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 26:419–424PubMedCrossRef 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 26:419–424PubMedCrossRef
15.
Zurück zum Zitat Sethi S, Fervenza C (2012) Membranoproliferative glomerulonephritis. A new look at an old entity. N Engl J Med 366:1119–1131PubMedCrossRef Sethi S, Fervenza C (2012) Membranoproliferative glomerulonephritis. A new look at an old entity. N Engl J Med 366:1119–1131PubMedCrossRef
16.
Zurück zum Zitat 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 46:2801–2807PubMedCrossRef 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 46:2801–2807PubMedCrossRef
17.
Zurück zum Zitat 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 69:981–988PubMedCrossRef 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 69:981–988PubMedCrossRef
18.
Zurück zum Zitat Lorcy N, Rioux-Leclercq N, Lombard ML, Le Pogamp P, Vigneau C (2011) Three kidneys, two diseases, one antibody? Nephrol Dial Transplant 26:3811–3813PubMedCrossRef Lorcy N, Rioux-Leclercq N, Lombard ML, Le Pogamp P, Vigneau C (2011) Three kidneys, two diseases, one antibody? Nephrol Dial Transplant 26:3811–3813PubMedCrossRef
19.
Zurück zum Zitat 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 51:671–677PubMedCrossRef 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 51:671–677PubMedCrossRef
20.
Zurück zum Zitat 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 23:137–148PubMedCrossRef 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 23:137–148PubMedCrossRef
21.
Zurück zum Zitat 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 15:225–228PubMedCrossRef 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 15:225–228PubMedCrossRef
22.
Zurück zum Zitat Waters AM, Licht C (2011) aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol 26:41–57PubMedCrossRef Waters AM, Licht C (2011) aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol 26:41–57PubMedCrossRef
Metadaten
Titel
Membrano-proliferative glomerulonephritis, atypical hemolytic uremic syndrome, and a new complement factor H mutation: report of a case
verfasst von
Elisa Gnappi
Marco Allinovi
Augusto Vaglio
Elena Bresin
Annalisa Sorosina
Francesco P. Pilato
Landino Allegri
Lucio Manenti
Publikationsdatum
01.10.2012
Verlag
Springer-Verlag
Erschienen in
Pediatric Nephrology / Ausgabe 10/2012
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-012-2210-0

Weitere Artikel der Ausgabe 10/2012

Pediatric Nephrology 10/2012 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.