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Diagnostic challenges in hereditary transthyretin amyloidosis with polyneuropathy: avoiding misdiagnosis of a treatable hereditary neuropathy
  1. Andrea Cortese1,2,
  2. Elisa Vegezzi3,4,
  3. Alessandro Lozza1,
  4. Enrico Alfonsi1,
  5. Alessandra Montini1,
  6. Arrigo Moglia1,5,
  7. Giampaolo Merlini6⇑,
  8. Laura Obici6
  1. 1 IRCCS, C Mondino National Neurological Institute, Pavia, Italy
  2. 2 Molecular Neuroscience, University College London Institute of Neurology, London, UK
  3. 3 Neuroscience Consortium, University of Pavia, Monza Policlinico and Pavia Mondino, Pavia, Italy
  4. 4 Department of Neurology, Casimiro Mondino National Neurological Institute, Pavia, Italy
  5. 5 Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
  6. 6 Amyloidosis Research and Treatment Center, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy
  1. Correspondence to Professor Giampaolo Merlini, Amyloidosis Research and Treatment Centre, IRCCS Fondazione Policlinico San Matteo, via C.Golgi 19, 27100, Pavia, Italy; gmerlini{at}

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Hereditary transthyretin (ATTR) amyloidosis is a debilitating highly penetrant autosomal dominant disease leading to motor disability within 5 years and generally fatal within a decade without treatment.

In Italy, hereditary ATTR amyloidosis shows broad genetic and phenotypic variability.1 Peripheral nerve damage can be isolated, in the absence of cardiac and autonomic involvement. Such a presentation makes it often difficult to distinguish ATTR amyloidosis-related peripheral neuropathy from other acquired peripheral neuropathies of adulthood.

Nowadays, avoiding misdiagnosis of ATTR amyloidosis is of vital importance because diverse treatment options are available, including liver transplantation and anti-amyloidogenic therapies with tafamidis or diflunisal, which all appear to be particularly effective in early disease stages.

In this study, we aimed to assess frequency, type and causes of misdiagnosis of ATTR amyloidosis in Italy.

We reviewed the medical records of 150 patients with ATTR diagnosed at the Amyloid Research and Treatment Centre between 1999 and 2013. Hundred-four (73%) were male with an average age of onset of 61 years (31–86). Most frequent mutations were Val30Met (p.Val50Met) (39; 26%), Glu89Gln (p.Glu109Gln) (28; 19%), Phe64Leu (p.Phe84Leu) (20; 13%), Ile68Leu (p.Ile88Leu) (14; 9%), Thr49Ala (p.Thr69Ala)(2; 5%). We reviewed electrodiagnostic (EDx) studies of 19 patients misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and we assessed fulfilment of European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) EDx criteria for demyelination. We excluded from the analysis distal motor latency prolongation and distal compound motor action potential (CMAP) duration in the median nerve because of frequent median neuropathy at the wrist from carpal tunnel syndrome and conduction block in the tibial …

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