title: Hereditary amyloidosis caused by R554L fibrinogen Aα-chain mutation in a Spanish family and review of the literature.
abstract: BACKGROUND
  Hereditary amyloidosis with predominant renal disease can be caused by mutations in the gene encoding the fibrinogen Aα-chain (AFib). Here, we describe the clinical course of AFib amyloidosis associated with the rare R554L mutation, and the significance of extrarenal amyloid deposits and their possible influence on cardiovascular morbidity.
  
  
  METHODS
  We report on 101 members of a family after having conducted patient interviews, chart review, genetic testing, renal biopsies and assessment for extrarenal amyloid deposition.
  
  
  RESULTS
  Ten family members had chronic kidney disease with late-onset gross proteinuria and a variable course of declining renal function, starting in the fourth decade of life. In two affected living members, we identified the AFib R554L mutation. Renal biopsies from two affected members revealed almost complete obliteration of the mesangial glomerular architecture, although kidney function was only moderately impaired. There was neither evidence of extrarenal amyloidosis nor accelerated atherosclerosis.
  
  
  CONCLUSIONS
  Renal amyloidosis associated with the R554L AFib variant dominated the clinical picture in this family, which was similar to that associated with the much more prevalent E526V mutation. Although it has been hypothesized that vascular deposits of fibrinogen amyloid may be associated with accelerated atherosclerosis, there was no suggestion of this in this particular kindred.
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Haidinger
authors.forename: Johannes
authors.initials: J
authors.lastname: Werzowa
authors.forename: Renate
authors.initials: R
authors.lastname: Kain
authors.forename: Marlies
authors.initials: M
authors.lastname: Antlanger
authors.forename: Manfred
authors.initials: M
authors.lastname: Hecking
authors.forename: Stefan
authors.initials: S
authors.lastname: Pfaffenberger
authors.forename: Julia
authors.initials: J
authors.lastname: Mascherbauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Gremmel
authors.forename: Janet A
authors.initials: JA
authors.lastname: Gilbertson
authors.forename: Dorota
authors.initials: D
authors.lastname: Rowczenio
authors.forename: Thomas
authors.initials: T
authors.lastname: Weichhart
authors.forename: Chantal
authors.initials: C
authors.lastname: Kopecky
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
mesh_terms: D000368:Aged; D000682:Amyloid / Q000235:genetics*; D028226:Amyloidosis, Familial / Q000175:diagnosis / Q000209:etiology*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000473:pathology; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000628:therapy; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology / Q000473:pathology; D012196:Review Literature as Topic; D013030:Spain
chemical_list: D000682:Amyloid; C464794:fibrinogen Aalpha; D005340:Fibrinogen