Different types of glomerulonephritis associated with the dysregulation of the complement alternative pathway in 2 brothers: A case report

Medicine (Baltimore). 2017 Jun;96(24):e7144. doi: 10.1097/MD.0000000000007144.

Abstract

Rationale: C3 glomerulonephritis (C3GN) and complement-mediated hemolytic uremic syndrome (HUS) both result from the abnormal regulation of the complement system. A significant number of patients with C3GN or complement-mediated HUS have mutations of more than 1 complement protein. This discovery has had a major impact on identifying the underlying cause of familial C3GN or complement-mediated HUS.

Patient concerns: We report the cases of 2 brothers (herein referred to as patient II-1 and patient II-9), both with complement disorders that differed in their clinical and genetic features.

Diagnoses: Patient II-1 clinically presented with nephrotic syndrome and acute kidney injury and pathologically presented with C3GN combined with thrombotic microangiopathy (TMA) and subacute tubulointerstitial nephritis. Meanwhile, patient II-9 clinically presented with HUS and pathologically presented with TMA combined with acute severe tubular injury.

Interventions: Screenings for genetic mutations contributed to complement system dysregulation were performed on patient II-1.

Outcomes: The genome sequencing identified that patient II-1 had a heterozygous mutation in the C3 gene (c.C1774T/p.R592W). Nine other relatives of the brothers were checked for this C3 mutation and only the daughter of patient II-1 (herein referred to as patient III-2) carried it, but so far, she does not have any clinical manifestations of kidney disease.

Lessions: Family members with a dysregulation of the complement alternative pathway may differ in its clinical and genetic features.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Complement Pathway, Alternative*
  • Complement System Proteins / genetics*
  • Complement System Proteins / metabolism*
  • Fatal Outcome
  • Glomerulonephritis / genetics*
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Glomerulonephritis / therapy
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Siblings

Substances

  • Complement System Proteins