Hereditary transthyretin amyloidosis in middle-aged and elderly patients with idiopathic polyneuropathy: a nationwide prospective study

AbstractBackground Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from TTR gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available.Methods In this 5 year-long (2017–2021) nationwide prospective study, we systematically analysed the TTR gene in French patients with age >50 years with a progressive idiopathic polyneuropathy.Results 553 patients (70% males) with a mean age of 70 years were included. A TTR gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met TTR variation in 10 cases. In comparison with patients with no TTR gene pathogenic variants (n = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, p = .007), significant weight loss (33 vs 11%, p = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, p = .03). ATTRv diagnosis led to amyloid cardiomyopathy diagnosis in 11 cases, ATTRv specific treatment in all cases and identification of 15 additional ATTRv cases among relatives.Conclusion In this nationwide prospective study, we found ATTRv in 2.7% of patients with age >50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.Keywords: AmyloidosisepidemiologyneuropathytransthyretinTTR gene AcknowledgmentsWe would like to thank the participants of the ADDITION study, The Research Unit Center, the Biological Resource Center Paris-Saclay (BCR Paris-Saclay) for the storage of ADDITION biological samples (BRIF number: BB-0033-00089).Disclosure statementProf Echaniz-Laguna received consulting fees from Alnylam Pharmaceuticals, Akcea Therapeutics, Astra Zeneca, and Pfizer. Docteur Labeyrie received consulting fees and speech honorarium from Alnylam Pharmaceuticals and Pfizer. Dr Svahn received speech honorarium and travel support from Alnylam France and Pfizer. Pr Philippe Camdessanché received fees for lectures, consulting, writing of articles, or training courses from Akcea, Alexion, Alnylam, Argenx, Biogen, Bristol Myers Squibb, CSL-Behring, Genzyme, Grifols, LFB, Merck, Novartis, Pfizer, Pharmalliance, Teva, UCB Pharma, Editions Scientifiques L&C, Edimark, Expression Santé, Natus, Scien, SNF-Floerger. Jean-Philippe Camdessanché have submitted a patent application for the application of FGFR3 and AGO antibodies as biomarkers. Jean-Philippe Camdessanché declare no disclosure for this article. Pr Cintas received consulting fees from Alnylam Pharmaceuticals, Akcea Therapeutics, and Pfizer. Dr. Chanson received consulting fees from Alnylam, non-financial support (hospitality) from LFB, Alexion, Sanofi-Genzyme, UCB, Alnylam, Pfizer and CSL-Behring, outside the submitted work. Dr Esselin received speech honorarium from Alnylam. Dr Genestet received travel support from Pfizer and Alnylam. Dr Lagrange disclosed conflict of interest with Pfizer. Pr Magy received travel expenses and/or housing and/or fees for consultancy in the last 3 years from Pfizer and Alnylam. Pr Péréon received consulting fees from Alnylam Pharmaceuticals, Akcea Therapeutics, Astra Zeneca, and Pfizer. Dr Sacconi disclosed conflict of interest with Pfizer. Dr Signate disclosed conflict of interest with Pfizer. Dr. Taithe received grants, non-personal consulting fees and travel fees from Alnylam and Pfizer. Dr. Tard reports personal fees and non-financial support from Pfizer, Alnylam, Sanofi-Genzyme, Roche, Biogen, UCB, Argenx, Alexion, LFB, outside the submitted work; personal fees from Akcea, Ultragenyx, non-financial support from Santhera. Dr Cauquil received consulting fees and speech honorarium from Pfizer, Alnylam Pharmaceuticals, Astrazeneca. Pr Attarian received speech honorarium and travel fees from Pfizer, Alnylam and AstraZeneca. Pr Adams received consulting fees from Pfizer, Alnylam, Astrazeneca, Bridgebio and payment of transport costs for ISA congress from Alnylam. The authors GF, CV, CP, KV, VP, A N-P and declare that they have no competing interest.Additional informationFundingThis work was supported by a Pfizer research grant [ID# 53232309]. However, Pfizer Inc. did not have influence on study design, data processing, and statistical analysis.