Regional difference and similarity of familial amyloidosis with polyneuropathy in France

Abstract

Familial amyloidosis with polyneuropathy (FAP) in France have a large genetic heterogeneity with 29 transthyretin (TTR) gene mutations; Met30-TTR is the most frequent one (62%); followed by Tyr77-TTR (11.8%) and Phe77-TTR (6.2%). Analysis of 60 FAP patients diagnosed during the period 2008-2010 showed amyloid polyneuropathy was initially suspected in only 38% patients. TTR Met30 of Portuguese ancestry is different from TTR Met30 of non Portuguese ancestry and other non Met30 variants in geographical distribution and clinical presentation. There are three additional phenotypes of the neuropathy including multifocal upper limbs neuropathy, ataxic polyneuropathy and motor neuropathy. Patients with Tyr77-TTR are characterized by a late onset (>50 years), frequent ataxic phenotype; they are localized mainly in north of France. The more frequent use of the TTR genetic tests and the French network for FAP will help in the future to improve diagnosis and care.