title: Variable presentations of TTR-related familial amyloid polyneuropathy in seventeen patients.
abstract: 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.
authors.affiliation: Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Verona.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cappellari
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cavallaro
authors.forename: Moreno
authors.initials: M
authors.lastname: Ferrarini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cabrini
authors.forename: Federica
authors.initials: F
authors.lastname: Taioli
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.forename: Laura
authors.initials: L
authors.lastname: Obici
authors.forename: Chiara
authors.initials: C
authors.lastname: Briani
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fabrizi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D001706:Biopsy; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000175:diagnosis; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000175:diagnosis; D011228:Prealbumin / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D011228:Prealbumin