Familial amyloidosis with polyneuropathy associated with TTR Ser50Arg mutation

Amyloid. 2012 Dec;19(4):171-6. doi: 10.3109/13506129.2012.712925. Epub 2012 Aug 28.

Abstract

Background: The phenotypic heterogeneity of transthyretin amyloidosis (ATTR) familial polyneuropathy may be linked to the type of mutation and to the environmental factors. A gender difference in relation to the severity of the disease has been suspected. More than 100 different pathogenic variants of hereditary transthyretin (TTR) mutations have been reported.

Objective: To describe 32 patients with confirmed TTR Ser50Arg mutation from the same geographical origin.

Methods: Seven families with up to four affected generations underwent genetic testing and prospective clinical and laboratory evaluations.

Results: The mutation was confirmed in seven patients from different families with clinical symptoms compatible with ATTR amyloidosis, and in 25 (62%) of the 40 direct relatives tested. Of the 32 patients with positive test results, 18 (56%) were men. Only 5 (16%) subjects were disease-free at the time of the genetic test (mean age: 20, range: 18-30-year-old). The rest developed symptoms at a young age, between ages 36 and 41. Symptomatic, histologically positive patients were older than carriers and symptomatic patients without a confirmatory biopsy. The later generation displayed symptoms at a younger age. Initial manifestations in the 27 symptomatic patients were neuropathic in 19 (70%), gastrointestinal in 6 (22%) and autonomic in 1 (4%). Significant differences were demonstrated among genders, where men had a considerably worse outcome.

Conclusion: ATTR Ser50Arg mutation was associated with an early onset, an unbalanced male to female ratio, a more aggressive course in males and possibly displayed anticipation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Amyloid / genetics*
  • Amyloidosis, Familial / complications
  • Amyloidosis, Familial / epidemiology*
  • Amyloidosis, Familial / genetics*
  • Biopsy
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Mutation*
  • Pedigree
  • Polyneuropathies / complications
  • Polyneuropathies / epidemiology*
  • Polyneuropathies / genetics*
  • Prealbumin / genetics*
  • Sex Factors

Substances

  • Amyloid
  • Prealbumin
  • transthyretin-related amyloid fibril protein, human