title: Unrecognized Fibrinogen A α-Chain Amyloidosis: Results From Targeted Genetic Testing.
abstract: BACKGROUND
  Fibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases.
  
  
  METHODS
  Case series.
  
  
  METHODS
  3 groups of participants: (1) kidney biopsy registry, n=4; (2) hemodialysis facility, n=122 of 267 patients; and (3) genetically at-risk individuals; n=69 of 167 family members.
  
  
  RESULTS
  Kidney disease, kidney disease progression, and survival.
  
  
  RESULTS
  The p.Glu545Val variant was identified in all 4 patients of the biopsy registry, 12 of 122 (9.8%) hemodialysis patients tested, and 34 of 69 (49%) relatives tested. These 50 cases belonged to 13 unrelated families with kidney disease or amyloidosis identified in 61% of probands. 35 individuals presented with hypertension at a mean of 51.0±10.4 years. Of these, 30 developed kidney disease at a mean of 56.7±12.0 years, and 21 initiated dialysis therapy at a mean of 61.4±11.3 years. Heart, liver, spleen, colon, and ileum were involved along the progression of the disease. Kidney disease was formerly attributed to hypertension in 25% of patients with AFib amyloidosis undergoing hemodialysis.
  
  
  CONCLUSIONS
  Retrospective data collection for patients with amyloidosis previously diagnosed.
  
  
  CONCLUSIONS
  AFib amyloidosis appears to be an under-recognized disorder in Braga, Portugal, where we found a high frequency of the FGA p.Glu545Val variant. Due to the nonspecific nature of its major clinical features, the diagnosis of AFib amyloidosis should have a high index of suspicion, particularly in populations in which hypertension is prevalent.
authors.affiliation: Department of Nephrology, Centro Hospitalar de São João, Porto, Portugal; Group of Research and Development in Nephrology and Infectious Diseases, Institute of Biomedical Engineering-I(3)S, University of Porto, Porto, Portugal. Electronic address: isabel.salome@hsjoao.min-saude.pt.
authors.forename: Isabel
authors.initials: I
authors.lastname: Tavares
authors.affiliation: Group of Research and Development in Nephrology and Infectious Diseases, Institute of Biomedical Engineering-I(3)S, University of Porto, Porto, Portugal; Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Oliveira
authors.affiliation: Department of Nephrology, Centro Hospitalar de São João, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Pinho
authors.affiliation: Department of Human Genetics, National Health Institute Doutor Ricardo Jorge, Porto, Portugal.
authors.forename: Luciana
authors.initials: L
authors.lastname: Moreira
authors.affiliation: Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Liliana
authors.initials: L
authors.lastname: Rocha
authors.affiliation: Department of Nephrology, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal; Dialysis Clinic of Braga, NephroCare-Portugal, Braga, Portugal.
authors.forename: Josefina
authors.initials: J
authors.lastname: Santos
authors.affiliation: Dialysis Clinic of Fafe, NephroCare-Portugal, Fafe, Portugal.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Pinheiro
authors.affiliation: Department of Human Genetics, National Health Institute Doutor Ricardo Jorge, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
authors.forename: Paulo Pinho
authors.initials: PP
authors.lastname: Costa
authors.affiliation: Department of Nephrology, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Lobato
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies
chemical_list: C464794:fibrinogen Aalpha; D005340:Fibrinogen
keywords: Amyloidosis; FGA p.Glu545Val; Portugal; chronic kidney disease (CKD); end-stage renal disease (ESRD); fibrinogen A alpha-chain; genetic screening; hemodialysis; hypertension; mutation; proteinuria