title: Homozygosity for the E526V Mutation in Fibrinogen A Alpha-Chain Amyloidosis: The First Report.
abstract: Systemic hereditary amyloidoses are autosomal dominant diseases associated with mutations in genes encoding ten different proteins. The clinical phenotype has implications on therapeutic approach, but it is commonly variable and largely dependent on the type of mutation. Except for rare cases involving gelsolin or transthyretin, patients are heterozygous for the amyloidogenic variants. Here we describe the first patient identified worldwide as homozygous for a nephropathic amyloidosis, involving the fibrinogen variant associated with the fibrinogen alpha-chain E526V (p.Glu545Val) mutation. In 1989, a 44-year-old woman presented with hypertension, hepatosplenomegaly, nephrotic syndrome, and renal failure. She started hemodialysis in 1990 and 6 years later underwent isolated kidney transplantation from a deceased donor. Graft function and clinical status were unremarkable for 16 years, despite progressively increased left ventricular mass on echocardiography. In 2012, 4 months before death, she deteriorated rapidly with severe heart failure, precipitated by Clostridium difficile colitis and urosepsis. Affected family members developed nephropathy, on average, nearly three decades later, which may be explained by the gene dosage effects on the phenotype of E526V (p.Glu545Val) fibrinogen A alpha-chain amyloidosis.
authors.affiliation: Department of Nephrology, Centro Hospitalar de São João, 4200-319 Porto, Portugal ; Nephrology and Infectious Diseases Research and Development Group, INEB (I3S), University of Porto, 4150-180 Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Tavares
authors.affiliation: Department of Nephrology, Centro Hospitalar do Porto, Hospital de Santo António, 4099-001 Porto, Portugal ; Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Lobato
authors.affiliation: Department of Nephrology, Centro Hospitalar do Porto, Hospital de Santo António, 4099-001 Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Matos
authors.affiliation: Department of Nephrology, Centro Hospitalar do Porto, Hospital de Santo António, 4099-001 Porto, Portugal ; Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal.
authors.forename: Josefina
authors.initials: J
authors.lastname: Santos
authors.affiliation: Molecular Neurobiology, Institute of Molecular and Cellular Biology, University of Porto, 4150-180 Porto, Portugal.
authors.forename: Paul
authors.initials: P
authors.lastname: Moreira
authors.affiliation: Molecular Neurobiology, Institute of Molecular and Cellular Biology, University of Porto, 4150-180 Porto, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Saraiva
authors.affiliation: Department of Nephrology, Centro Hospitalar do Porto, Hospital de Santo António, 4099-001 Porto, Portugal ; Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Castro Henriques