HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 69, Number 07, August 14, 2007 Data Supplement Correspondence: Submit a response Correspondence: View responses Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Planté-Bordeneuve, V. Articles by Said, G. Search for Related Content PubMed PubMed Citation Articles by Planté-Bordeneuve, V. Articles by Said, G. Related Collections Peripheral neuropathy Chronic inflammatory demyelinating polyneuropathy All Genetics Related Article

Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP)

From the Centre d’Etude des Neuropathies Amyloïdes Familiales, Service de Neurologie, and Laboratoire Ranvier, Inserm U 788, Hôpital de Bicêtre Assistance Publique Hôpitaux de Paris, Université Paris-Sud, France.

Address correspondence and reprint requests to Dr. V. Planté, Service de Neurologie, Hôpital de Bicêtre, 94275 Le Kremlin Bicêtre, France violaine.plante{at}bct.aphp.fr

Transthyretin familial amyloid polyneuropathies (TTR-FAPs) are autosomal dominant neuropathies of fatal outcome within 10 years after inaugural symptoms. Late diagnosis in patients who present as nonfamilial cases delays adequate management and genetic counseling. Clinical data of the 90 patients who presented as nonfamilial cases of the 300 patients of our cohort of patients with TTR-FAP were reviewed. They were 21 women and 69 men with a mean age at onset of 61 (extremes: 38 to 78 years) and 17 different mutations of the TTR gene including Val30Met (38 cases), Ser77Tyr (16 cases), Ile107Val (15 cases), and Ser77Phe (5 cases). Initial manifestations included mainly limb paresthesias (49 patients) or pain (17 patients). Walking difficulty and weakness (five patients) and cardiac or gastrointestinal manifestations (five patients), were less common at onset. Mean interval to diagnosis was 4 years (range 1 to 10 years); 18 cases were mistaken for chronic inflammatory demyelinating polyneuropathy, which was the most common diagnostic error. At referral a length-dependent sensory loss affected the lower limbs in 2, all four limbs in 20, and four limbs and anterior trunk in 77 patients. All sensations were affected in 60 patients (67%), while small fiber dysfunction predominated in the others. Severe dysautonomia affected 80 patients (90%), with postural hypotension in 52, gastrointestinal dysfunction in 50, impotence in 58 of 69 men, and sphincter disturbance in 31. Twelve patients required a cardiac pacemaker. Nerve biopsy was diagnostic in 54 of 65 patients and salivary gland biopsy in 20 of 30. Decreased nerve conduction velocity, increased CSF protein, negative biopsy findings, and false immunolabeling of amyloid deposits were the main causes of diagnostic errors. We conclude that DNA testing, which is the most reliable test for TTR-FAP, should be performed in patients with a progressive length-dependent small fiber polyneuropathy of unknown origin, especially when associated with autonomic dysfunction.

Supplemental data at www.neurology.org

Editorial, see page 627

Disclosure: The authors report no conflicts of interest.

Received September 6, 2006. Accepted in final form March 14, 2007.

Related Article

Is familial amyloid polyneuropathy rare?: DNA testing is changing the concept of this disease

Shu-ichi Ikeda
Neurology 2007 69: 627-628. [Full Text] [PDF]

This article has been cited by other articles:

				K. Ikeda, O. Kano, H. Ito, Y. Kawase, K. Iwamoto, R. Sato, T. Sekine, R. Nagata, Y. Nakamura, T. Hirayama, et al. Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP) Neurology, April 22, 2008; 70(17): 1576 - 1577. [Full Text] [PDF]

Correspondence: