title: Hereditary ATTR amyloidosis: a single-institution experience with 266 patients.
abstract: BACKGROUND
  Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a rare, clinically heterogeneous disease due to heritable mutations that lead to misfolding of a precursor protein and multisystem disease. This study sought to define the clinical characteristics, distribution of mutations and phenotypic presentation of patients presenting to our center with hereditary ATTR amyloidosis.
  
  
  METHODS
  With institutional review board approval, the study retrospectively identified patients who had hereditary ATTR amyloidosis and presented to Mayo Clinic in Rochester, Minnesota, from 1 January 1970, to 29 January 2013.
  
  
  RESULTS
  Of the 266 patients with the diagnosis of hereditary ATTR amyloidosis, a pathogenic mutation was identified in 206; the most common mutation was Thr60Ala (68 patients [25%]). Median age at diagnosis was 63.3 years; median survival after diagnosis was 56.8 months (10th-90th percentile, 16.0-297.9). On multivariate analysis, age at diagnosis (risk ratio, 15.65; p < 0.0001), Thr60Ala mutation (risk ratio, 1.52; p = 0.04), Val122Ile mutation (risk ratio, 2.83; p = 0.003), peripheral neuropathy (risk ratio, 1.69; p = 0.013) and weight loss (risk ratio, 1.81; p = 0.002) were risk factors for death.
  
  
  CONCLUSIONS
  Our data characterize the features of hereditary ATTR amyloidosis in a large cohort, demonstrate the heterogeneity among mutations and support the need to better characterize the clinical progression of individual mutations.
authors.affiliation: Department of Internal Medicine .
authors.forename: Paul L
authors.initials: PL
authors.lastname: Swiecicki
authors.forename: David B
authors.initials: DB
authors.lastname: Zhen
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Mauermann
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Steven R
authors.initials: SR
authors.lastname: Zeldenrust
authors.forename: Martha
authors.initials: M
authors.lastname: Grogan
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000235:genetics*; D028226:Amyloidosis, Familial / Q000235:genetics; D009202:Cardiomyopathies / Q000235:genetics; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics; D011228:Prealbumin / Q000235:genetics*
chemical_list: D011228:Prealbumin
keywords: Cardiomyopathy; mutation; peripheral neuropathy; phenotype; transthyretin