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Variable presentations of TTR‐related familial amyloid polyneuropathy in seventeen patients
Author(s) -
Cappellari Manuel,
Cavallaro Tiziana,
Ferrarini Moreno,
Cabrini Ilaria,
Taioli Federica,
Ferrari Sergio,
Merlini Giampaolo,
Obici Laura,
Briani Chiara,
Fabrizi Gian Maria
Publication year - 2011
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1529-8027.2011.00331.x
Subject(s) - transthyretin , amyloid polyneuropathy , amyloid (mycology) , polyneuropathy , medicine , amyloidosis , pathology , age of onset , disease
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.