title: Clinical and genetic findings in eight Israeli patients with transthyretin-associated familial amyloid polyneuropathy.
abstract: BACKGROUND
  Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological manifestations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid.
  
  
  OBJECTIVE
  To describe the clinical and genetic findings in patients with TTR-associated FAP in Israel.
  
  
  METHODS
  We evaluated eight patients clinically and genetically during the years 2006 to 2011.
  
  
  RESULTS
  At onset, all the patients exhibited sensory loss of the lower and upper limbs, five patients experienced muscle pain, and one patient had lower limb weakness. Five patients had autonomic nervous system manifestations, and four demonstrated evidence of amyloid cardiomyopathy. Nerve conduction studies showed sensorimotoraxonal neuropathy in all patients. Sural nerve biopsies were obtained in five patients; only three biopsies revealed amyloid deposit. In four patients of Yemenite descent, genetic analysis of the TTR gene demonstrated ser77tyr mutation. One patient of Tunisian descent and one Ashkenazi patient harbored the val30met mutation. One patient of Iranian descent showed val32ala mutation, and another Ashkenazi patient showed phe33leu mutation.
  
  
  CONCLUSIONS
  TTR-associated FAP is a progressive and fatal disease that exists in the Israeli population and is unproportionally common among Yemenite Jews. This disease may be under-diagnosed and should be considered in the differential diagnosis of any patient with rapidly progressive neuropathy, especially with autonomic involvement or extra-neural features. The absence of amyloid in nerve biopsy should not rule out the diagnosis.
authors.affiliation: Plastic Surgery Unity, Wolfson Medical Center, Holon, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Leibou
authors.forename: Jacob
authors.initials: J
authors.lastname: Frand
authors.forename: Menachem
authors.initials: M
authors.lastname: Sadeh
authors.forename: Alexander
authors.initials: A
authors.lastname: Lossos
authors.forename: Eyal
authors.initials: E
authors.lastname: Kremer
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
authors.forename: David
authors.initials: D
authors.lastname: Yarnitsky
authors.forename: Oscar
authors.initials: O
authors.lastname: Herman
authors.forename: Ron
authors.initials: R
authors.lastname: Dabby
mesh_terms: D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism; D015995:Prevalence; D012189:Retrospective Studies
chemical_list: D011228:Prealbumin; D004247:DNA