Hereditary ATTR amyloidosis: A single-institution experience with 266 patients

Paul L. Swiecicki, David B. Zhen, Michelle M Mauermann, Robert A. Kyle, Steven R. Zeldenrust, Martha Grogan, Angela Dispenzieri, Morie Gertz

Research output: Contribution to journalArticle

19 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalAmyloid
Volume22
Issue number2
DOIs
StatePublished - Jun 1 2015

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Familial Amyloidosis
Mutation
Odds Ratio
Hospital Distribution Systems
Protein Precursors
Research Ethics Committees
Peripheral Nervous System Diseases
Amyloidosis
Weight Loss
Multivariate Analysis

Keywords

  • Cardiomyopathy
  • Mutation
  • Peripheral neuropathy
  • Phenotype
  • Transthyretin

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Hereditary ATTR amyloidosis : A single-institution experience with 266 patients. / Swiecicki, Paul L.; Zhen, David B.; Mauermann, Michelle M; Kyle, Robert A.; Zeldenrust, Steven R.; Grogan, Martha; Dispenzieri, Angela; Gertz, Morie.

In: Amyloid, Vol. 22, No. 2, 01.06.2015, p. 123-131.

Research output: Contribution to journalArticle

Swiecicki, Paul L. ; Zhen, David B. ; Mauermann, Michelle M ; Kyle, Robert A. ; Zeldenrust, Steven R. ; Grogan, Martha ; Dispenzieri, Angela ; Gertz, Morie. / Hereditary ATTR amyloidosis : A single-institution experience with 266 patients. In: Amyloid. 2015 ; Vol. 22, No. 2. pp. 123-131.
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