title: Transthyretin-Related Familial Amyloid Polyneuropathy (TTR-FAP): A Single-Center Experience in Sicily, an Italian Endemic Area.
abstract: BACKGROUND
  Familial amyloid polyneuropathy related to transthyretin gene (TTR-FAP) is a life-threatening disease transmitted as an autosomal dominant trait. Val30Met mutation accounts for the majority of the patients with large endemic foci especially in Portugal, Sweden and Japan. However, more than one hundred other mutations have been described worldwide. A great phenotypic variability among patients with late- and early-onset has been reported.
  
  
  OBJECTIVE
  To present a detailed report of TTR-FAP patients diagnosed in our tertiary neuromuscular center, in a 20-year period.
  
  
  METHODS
  Clinical informations were gathered through the database of our center.
  
  
  RESULTS
  The study involved 76 individuals carrying a TTR-FAP mutation. Three phenotypes were identified, each corresponding to a different TTR variant, homogeneous within and heterogeneous between each other: i) Glu89Gln mutation, characterised by 5th - 6th decade onset, neuropathy as presenting symptoms, early heart dysfunction, cardiomyopathy as major cause of mortality followed by dysautonomia and cachexia; ii) Phe64Leu mutation, marked by familiarity reported in one-half of cases, late onset, severe peripheral neuropathy, moderate dysautonomia and mild cardiomyopathy, death for wasting syndrome; iii) Thr49Ala mutation, distinguished by onset in the 5th decade, autonomic disturbances as inaugural symptoms which may remain isolated for many years, moderate polyneuropathy, cachexia as major cause of mortality followed by cardiomyopathy.
  
  
  CONCLUSIONS
  This survey highlighted a prevalence of 8.8/1,000,000 in Sicily Island. Good knowledge of the natural history of the disease according to different TTR mutations allow clinicians to optimise multiprofessional care for patients and to offer carriers a personalized follow-up to reveal first signs of the disease.
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mazzeo
authors.affiliation: NEMO SUD Center for Neuromuscular Disorders, Messina, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Russo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Di Bella
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, Messina, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Minutoli
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.|Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Palermo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Stancanelli
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Gentile
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, Messina, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Baldari
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Scipione
authors.initials: S
authors.lastname: Carerj
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Toscano
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.|NEMO SUD Center for Neuromuscular Disorders, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vita
keywords: FAP; Familial amyloid polyneuropathy; Italy; TTR; amyloidosis; cardiomyopathy; dysautonomia; epidemiology; transthyretin