Variable presentations of TTR-related familial amyloid polyneuropathy in seventeen patients

Manuel Cappellari, Tiziana Cavallaro, Moreno Ferrarini, Ilaria Cabrini, Federica Taioli, Sergio Ferrari, Giampaolo Merlini, Laura Obici, Chiara Briani, Gian Maria Fabrizi

Research output: Contribution to journalArticlepeer-review


Autosomal-dominant transthyretin (TTR)-related amyloidosis usually manifests in the second to fourth decade with a length-dependent axonal neuropathy with prominent involvement of the small fibers and multi-organ systemic failure. We retrospectively analyzed seventeen probands, including thirteen apparently isolated cases, carrying eight mutations of TTR gene (age of onset = 60.4 ± 13.5 years). Thirteen patients were initially un/misdiagnosed; interval from onset to definite diagnosis was 3.3 ± 2.3 years. Inaugural syndromes were a length-dependent motor-sensory neuropathy in seven cases, a sensory neuropathy in four, an isolated carpal tunnel syndrome in three, a pure dysautonomia in two, and a painful neuropathy in one. Atypical presentations included demyelinating nerve conduction changes with increased cerebrospinal fluid proteins resembling chronic inflammatory demyelinating polyradiculoneuropathy and a predominantly motor involvement resembling a motor neuron disorder. Misleading findings also included amyloid-negative abdominal fat aspirate/biopsy, biclonal gammopathy, and hepatitis C virus (HCV) seropositivity. Sural nerve biopsy detected amyloid deposits in thirteen of fifteen patients, including one case with a previous negative biopsy. TTR-immunohistochemistry was necessary to complete the diagnosis of primary amyloidosis light chain in a patient with biclonal gammopathy. A recurrent p.Phe64Leu mutation manifested in the seventh decade with painful motor-sensory polyneuropathy, dysautonomia, bulbar palsies, and fasciculations. TTR should be tested in a wide clinical spectrum of cryptogenetic, progressive, and motor-sensory neuropathies even manifesting with a very late onset.

Original languageEnglish
Pages (from-to)119-129
Number of pages11
JournalJournal of the Peripheral Nervous System
Issue number2
Publication statusPublished - Jun 2011


  • Amyloid
  • Familial amyloid polyneuropathy
  • Transthyretin

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Medicine(all)


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