Childhood Kidney Diseases

Korean Society of Pediatric Nephrology (대한소아신장학회)
권호 표지
DOI QR코드

DOI QR Code

C3 glomerulonephritis with genetically confirmed C3 deficiency in a pediatric patient: a case report

  • Hae Min Kim (Department of Pediatrics, Yonsei University College of Medicine) ;
  • Jae Il Shin (Department of Pediatrics, Yonsei University College of Medicine) ;
  • Ji Hong Kim (Department of Pediatrics, Yonsei University College of Medicine) ;
  • Jiyoung Oh (Department of Pediatrics, Yonsei University College of Medicine) ;
  • Ji-Man Kang (Department of Pediatrics, Yonsei University College of Medicine) ;
  • Hee Gyung Kang (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Seong Heon Kim (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Byoung Soo Cho (Dr. Cho's Kidney Clinic) ;
  • Keum Hwa Lee (Department of Pediatrics, Yonsei University College of Medicine)
  • Received : 2024.09.13
  • Accepted : 2024.10.14
  • Published : 2024.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Complement component 3 glomerulonephritis (C3GN) is a rare kidney disease characterized by complement dysregulation that results in prominent complement component 3 (C3) deposition in the kidneys. The clinical course of C3GN varies from mild hematuria to progressive chronic kidney disease. In most patients, C3GN is driven by acquired factors, namely, autoantibodies that target C3 or C5 convertases. Genetic variations in complement-related genes are less frequent. We report the case of a 9-year-old Korean boy who presented with microscopic hematuria and a persistently low C3 level and had biopsy findings of C3GN, with the presence of a C3 gene mutation: a frameshift mutation associated with C3 deficiency. However, the patient did not exhibit any other symptoms of complement deficiency. Direct DNA sequencing of his family members revealed the same genetic mutation in his father and older brother. This case report is significant because there are very few such reports worldwide concerning gene mutations related to C3 deficiency to be discovered in patients with C3GN. Explaining C3GN pathogenesis is challenging; therefore, additional research is required in the future.

Keywords

References

  1. Kim YJ. Pathology of C3 glomerulonephritis. J Korean Soc Pediatr Nephrol 2013;17:1-5.  https://doi.org/10.3339/jkspn.2013.17.1.1
  2. Appel GB. C3 glomerulopathy: a new disease comes of age. Mayo Clin Proc 2018;93:968-9.  https://doi.org/10.1016/j.mayocp.2018.06.014
  3. Sethi S, Fervenza FC, Zhang Y, Zand L, Vrana JA, Nasr SH, et al. C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int 2012;82:465-73.  https://doi.org/10.1038/ki.2012.212
  4. Smith RJH, Appel GB, Blom AM, Cook HT, D'Agati VD, Fakhouri F, et al. C3 glomerulopathy: understanding a rare complement-driven renal disease. Nat Rev Nephrol 2019;15:129-43.  https://doi.org/10.1038/s41581-018-0107-2
  5. Servais A, Noel LH, Fremeaux-Bacchi V, Lesavre P. C3 glomerulopathy. Contrib Nephrol 2013;181:185-93.  https://doi.org/10.1159/000348654
  6. Ravindran A, Fervenza FC, Smith RJH, De Vriese AS, Sethi S. C3 glomerulopathy: ten years' experience at Mayo Clinic. Mayo Clin Proc 2018;93:991-1008.  https://doi.org/10.1016/j.mayocp.2018.05.019
  7. Schroder-Braunstein J, Kirschfink M. Complement deficiencies and dysregulation: Pathophysiological consequences, modern analysis, and clinical management. Mol Immunol 2019;114:299-311.  https://doi.org/10.1016/j.molimm.2019.08.002
  8. Martinez-Barricarte R, Heurich M, Valdes-Canedo F, Vazquez-Martul E, Torreira E, Montes T, et al. Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. J Clin Invest 2010;120:3702-12.  https://doi.org/10.1172/JCI43343
  9. Xiao X, Pickering MC, Smith RJ. C3 glomerulopathy: the genetic and clinical findings in dense deposit disease and C3 glomerulonephritis. Semin Thromb Hemost 2014;40:465-71.  https://doi.org/10.1055/s-0034-1376334
  10. Barbier M, Gross MS, Aubart M, Hanna N, Kessler K, Guo DC, et al. MFAP5 loss-of-function mutations underscore the involvement of matrix alteration in the pathogenesis of familial thoracic aortic aneurysms and dissections. Am J Hum Genet 2014;95:736-43.  https://doi.org/10.1016/j.ajhg.2014.10.018
  11. Li Y, Kong Y, Duan W, Yu S, Zhou X, Hu Y, et al. Evaluating the monogenic contribution and genotype-phenotype correlation in patients with isolated thoracic aortic aneurysm. Eur J Hum Genet 2021;29:1129-38.  https://doi.org/10.1038/s41431-021-00857-2
  12. Zhang H, Apfelroth SD, Hu W, Davis EC, Sanguineti C, Bonadio J, et al. Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices. J Cell Biol 1994;124:855-63.  https://doi.org/10.1083/jcb.124.5.855
  13. Okura Y, Kobayashi I, Yamada M, Sasaki S, Yamada Y, Kamioka I, et al. Clinical characteristics and genotype-phenotype correlations in C3 deficiency. J Allergy Clin Immunol 2016;137:640-4.  https://doi.org/10.1016/j.jaci.2015.08.017
  14. Kida M, Fujioka H, KosakaY,Hayashi K, SakiyamaY, Ariga T. The first confirmed case with C3 deficiency caused by compound heterozygous mutations in the C3 gene; a new aspect of pathogenesis for C3 deficiency. Blood Cells Mol Dis 2008;40:410-3.  https://doi.org/10.1016/j.bcmd.2007.11.002
  15. Bomback AS, Smith RJ, Barile GR, Zhang Y, Heher EC, Herlitz L, et al. Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am Soc Nephrol 2012;7:748-56. https://doi.org/10.2215/CJN.12901211