Hereditary transthyretin-related amyloidosis is frequent in polyneuropathy and cardiomyopathy of no obvious aetiology
Creators: name: Skrahina, Volha
name: Grittner, Ulrike
name: Beetz, Christian
name: Skripuletz, Thomas
name: Juenemann, Martin
name: Krämer, Heidrun H.
name: Hahn, Katrin
name: Rieth, Andreas
name: Schaechinger, Volker
name: Patten, Monica
name: Tanislav, Christian
name: Achenbach, Stephan
name: Assmus, Birgit
name: Knebel, Fabian
name: Gingele, Stefan
name: Skrahin, Aliaksandr
name: Hartkamp, Jörg
name: Förster, Toni M.
name: Roesner, Sabine
name: Pereira, Catarina
name: Rolfs, Arndt
Publisher: name: Taylor & Francis
Year: 2021
Subjects: Neuroscience
Biotechnology
Environmental Sciences not elsewhere classified
Biological Sciences not elsewhere classified
Science Policy
Mental Health

description: Hereditary Transthyretin-Related Amyloidosis, a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the <i>TTR</i> gene, is characterized by the deposition of insoluble misfolded protein fibrils. The diagnosis, especially in non-endemic areas, is typically delayed by 4–5 years; a misdiagnosis due to clinical heterogeneity is common. The study objective was to define the prevalence of Hereditary Transthyretin-Related Amyloidosis in patients with polyneuropathy and/or cardiomyopathy of no obvious aetiology. A multicenter observational “Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis”—TRAM study was performed in Germany, Austria, and Switzerland. A total of 5141 participants were recruited by 50 neurologic and 27 cardiologic specialized centres. Genetic analysis demonstrated a 1.1% Hereditary Transthyretin-Related Amyloidosis positivity rate among patients with polyneuropathy and/or cardiomyopathy of not obvious aetiology. Twenty-one various <i>TTR</i> variants (<i>TTR</i>-positive) were identified. Body Mass Index was lower in the <i>TTR</i>-positive patients as an indicator for the involvement of the autonomic nervous system; the age of onset of clinical manifestations was higher in <i>TTR</i>-positive patients. There were no other genotype-phenotype correlations or the prevalence of specific clinical manifestations in <i>TTR</i>-positive patients. Our data support the fact that Hereditary Transthyretin-Related Amyloidosis is underdiagnosed in polyneuropathy and cardiomyopathy patients. Routine implementation of genetic testing is recommended in patients with unexplained polyneuropathy and/or cardiomyopathy to accelerate the earlier diagnosis and the time-sensitive treatment initiation.KEY MESSAGESMore than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational “Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis” TRAM study and screened for pathogenic <i>TTR</i> variants.The study demonstrated &gt;1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic <i>TTR</i> variant.Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation. More than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational “Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis” TRAM study and screened for pathogenic <i>TTR</i> variants. The study demonstrated &gt;1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic <i>TTR</i> variant. Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation.