title: Familial amyloidosis with polyneuropathy type 1 caused by transthyretin mutation Val50Met (Val30Met): 4 cases in a non-endemic area.
abstract: BACKGROUND
  Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) typically arises as an autonomic neuropathy primarily affecting small fibres and it occurs in adult patients in their second or third decades of life. It progresses rapidly and can lead to death in approximately 10 years. Other phenotypes have been described in non-endemic areas.
  
  
  OBJECTIVE
  We described 4 cases from the Spanish province of Guipuzcoa, a non-endemic area, to highlight the clinical variability of this disease.
  
  
  RESULTS
  Three patients presented a late-onset form manifesting after the age of 50, featuring a predominantly motor polyneuropathy initially causing distal impairment of the lower limbs followed by the upper limbs. One patient suffered severe neuropathic pain. None showed signs of autonomic involvement. The fourth patient, of Portuguese descent, presented a typical form with onset in her thirties, neuropathic pain and dysautonomia. All patients carry the Val50Met mutation in the TTR gene.
  
  
  CONCLUSIONS
  FAP is a pleomorphic disease even in patients carrying the same mutation. In non-endemic areas, its main form of presentation may resemble a predominantly motor polyneuropathy developing in the sixth decade of life with no signs of dysautonomia. Given this non-specific presentation and the widely available technical means of studying the TTR gene, we believe that the protocol for the aetiological diagnosis of any polyneuropathy should include genetic sequencing of TTR.
authors: Servicio de Neurología, Hospital Universitario Donostia, San Sebastián, España. Electronic address: naiara.andresmarin@osakidetza.eus.
authors: N
authors: N
authors: Andrés
authors: Servicio de Neurología, Hospital Universitario Donostia, San Sebastián, España.
authors: J J
authors: JJ
authors: Poza
authors: Servicio de Neurología, Hospital Universitario Donostia, San Sebastián, España; Área de Neurociencias, Universidad del País Vasco, San Sebastián, España.
authors: J F
authors: JF
authors: Martí Massó
mesh_terms: D000328:Adult; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000473:pathology; D028226:Amyloidosis, Familial / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011228:Prealbumin / Q000235:genetics*
chemical_list: D011228:Prealbumin
keywords: Amiloide; Amyloid; Hereditary amyloid polyneuropathy; Polineuropatía amiloidótica hereditaria; Transthyretin; Transtiretina; Val50Met (Val30Met)