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

Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from <i>TTR</i> gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available. In this 5 year-long (2017–2021) nationwide prospective study, we systematically analysed the <i>TTR</i> gene in French patients with age &gt;50 years with a progressive idiopathic polyneuropathy. 553 patients (70% males) with a mean age of 70 years were included. A <i>TTR</i> gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met <i>TTR</i> variation in 10 cases. In comparison with patients with no <i>TTR</i> gene pathogenic variants (<i>n</i> = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, <i>p</i> = .007), significant weight loss (33 vs 11%, <i>p</i> = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, <i>p</i> = .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. In this nationwide prospective study, we found ATTRv in 2.7% of patients with age &gt;50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.