title: Familial amyloidosis with polyneuropathy associated with TTR Ser50Arg mutation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico DF. gonzalezduarte@aol.com
authors.forename: Alejandra
authors.initials: A
authors.lastname: González-Duarte
authors.forename: Karla Cárdenas
authors.initials: KC
authors.lastname: Soto
authors.forename: Deborah
authors.initials: D
authors.lastname: Martínez-Baños
authors.forename: Jazmin
authors.initials: J
authors.lastname: Arteaga-Vazquez
authors.forename: Fausto
authors.initials: F
authors.lastname: Barrera
authors.forename: Mauricio
authors.initials: M
authors.lastname: Berenguer-Sanchez
authors.forename: Carlos
authors.initials: C
authors.lastname: Cantu-Brito
authors.forename: Guillermo
authors.initials: G
authors.lastname: García-Ramos
authors.forename: Bruno
authors.initials: B
authors.lastname: Estañol Vidal
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000682:Amyloid / Q000235:genetics*; D028226:Amyloidosis, Familial / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D001706:Biopsy; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011115:Polyneuropathies / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D011228:Prealbumin / Q000235:genetics*; D012737:Sex Factors
chemical_list: D000682:Amyloid; D011228:Prealbumin; C076571:transthyretin-related amyloid fibril protein, human