Late-onset hereditary ATTR V30M amyloidosis with polyneuropathy: Characterization of Brazilian subjects from the THAOS registry

J Neurol Sci. 2019 Aug 15:403:1-6. doi: 10.1016/j.jns.2019.05.030. Epub 2019 May 28.

Abstract

Background: Despite growing numbers of patients diagnosed with late-onset hereditary ATTR V30M amyloidosis with polyneuropathy (ATTRv-PN), this condition remains poorly characterized in Brazil.

Objective: Characterize late-onset V30M ATTRv-PN in Brazil.

Material and methods: Demographic and clinical data at the time of enrolment for Brazilian subjects with symptomatic V30M ATTRv-PN were extracted from the ongoing, multinational, longitudinal, observational Transthyretin Amyloidosis Outcomes Survey (THAOS; cut-off date: January 30, 2017). Subjects were divided into those with symptom onset at age <50 years (EO-V30M), and at age ≥50 years (LO-V30M).

Results: A total of 96 Val30Met patients were symptomatic. LO-V30M (n = 25, 26.0%) had a longer time to diagnosis (mean 5.1 vs. 2.8 yrs.; p = 0.006) and less frequently positive family history (40% vs. 95.8%; p < 0.0001) than EO-V30M. Clinically, subjects with LO-V30M had more imbalance (92% vs. 54.9%; p = 0.006), deep sensory loss (100% vs. 80%; p = 0.0178), electrocardiogram abnormalities (88.9% vs. 59.4; p = 0.0241), and interventricular septum hypertrophy (69.2% vs. 0%; p < 0001) and less frequently sensory dissociation (12% vs. 74%; p < 0.0001). Also, LO-V30M tended to have more severe mean Neurologic Composite Score (101 vs. 70 pts.; p = 0.1136).

Conclusions: LO-V30M ATTRv-PN is not unusual in Brazil, tending to be more difficult to diagnose and present with a more severe phenotype, with more large nerve fibers and cardiac involvement than EO-V30M.

Trial registration: ClinicalTrials.gov: NCT00628745.

Keywords: Early-onset ATTRv-PN; Familial amyloid polyneuropathy; Hereditary transthyretin amyloidosis; Late-onset ATTRv-PN; Polyneuropathy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Amyloid Neuropathies, Familial / diagnostic imaging*
  • Amyloid Neuropathies, Familial / epidemiology*
  • Amyloid Neuropathies, Familial / genetics
  • Brazil / epidemiology
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Polyneuropathies / diagnostic imaging*
  • Polyneuropathies / epidemiology*
  • Polyneuropathies / genetics
  • Registries*

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Associated data

  • ClinicalTrials.gov/NCT00628745