{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:44:39Z","timestamp":1786553079694,"version":"build-2736575974"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["54551481"],"award-info":[{"award-number":["54551481"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Sci"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Early diagnosis of hereditary ATTR polyneuropathy (ATTRv-PN) is important since treatment options have become available, which are most effective early in the disease course. ATTRv-PN is likely underdiagnosed as patients might be misdiagnosed with idiopathic polyneuropathy. It is uncertain if it is useful to test for TTR gene mutations in patients with a typical presentation for chronic idiopathic axonal polyneuropathy (CIAP) and which are the distinguishing clinical features.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We carried out a retrospective cohort study to assess the yield of TTR gene sequencing in patients with polyneuropathy and assessed if the identified patients with ATTRv-PN had a clinical presentation typical of CIAP. Additionally, we assessed which clinical features, including previously defined red flag symptoms, can differentiate between patients with CIAP and ATTRv-PN and assessed the performance of the TTR suspicion index.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Out of 338 patients with polyneuropathy, 10 patients had a pathogenic TTR gene mutation (all p.Val50Met) and none had a clinical presentation typical of CIAP. Patients with ATTRv-PN more often had bilateral CTS, motor involvement of arms, cardiac involvement, family history suggestive of hATTRv, and autonomic symptoms than patients with CIAP. All patients with ATTRv-PN as well as 70% of patients with CIAP fulfilled the suspicion index.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Routine TTR gene sequencing in patients with a typical presentation for CIAP is not useful. However, red flag symptoms can differentiate patients with ATTRv-PN from patients with CIAP. We propose an adjusted version of the TTR suspicion index to increase diagnostic yield.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10072-023-06859-w","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T12:41:05Z","timestamp":1685709665000},"page":"3679-3685","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Red flags and adjusted suspicion index for distinguishing hereditary transthyretin amyloid polyneuropathy from idiopathic axonal polyneuropathy"],"prefix":"10.1007","volume":"44","author":[{"given":"Janna K.","family":"Warendorf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerjan M.","family":"van der Star","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Dooijes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolette C.","family":"Notermans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander F. J. E.","family":"Vrancken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"6859_CR1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1750-1172-8-31","volume":"8","author":"Y Ando","year":"2013","unstructured":"Ando Y, Coelho T, Berk JL et al (2013) Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis 8:31. https:\/\/doi.org\/10.1186\/1750-1172-8-31","journal-title":"Orphanet J Rare Dis"},{"key":"6859_CR2","doi-asserted-by":"publisher","first-page":"e01371","DOI":"10.1002\/brb3.1371","volume":"9","author":"MA Gertz","year":"2019","unstructured":"Gertz MA, Mauermann ML, Grogan M et al (2019) Advances in the treatment of hereditary transthyretin amyloidosis: A review. 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J Neurol 265:976\u2013983. https:\/\/doi.org\/10.1007\/s00415-017-8708-4","journal-title":"J Neurol"},{"key":"6859_CR5","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1212\/WNL.0000000000001160","volume":"84","author":"NA Visser","year":"2015","unstructured":"Visser NA, Notermans NC, Linssen RSN et al (2015) Incidence of polyneuropathy in Utrecht, the Netherlands. Neurology 84:259\u2013264. https:\/\/doi.org\/10.1212\/WNL.0000000000001160","journal-title":"Neurology"},{"key":"6859_CR6","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s10654-015-0094-6","volume":"31","author":"R Hanewinckel","year":"2016","unstructured":"Hanewinckel R, van Oijen M, Ikram MA et al (2016) The epidemiology and risk factors of chronic polyneuropathy. Eur J Epidemiol 31:5\u201320. https:\/\/doi.org\/10.1007\/s10654-015-0094-6","journal-title":"Eur J Epidemiol"},{"key":"6859_CR7","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1007\/s00415-020-09899-w","volume":"267","author":"B Vogt","year":"2020","unstructured":"Vogt B, Chahin N, Wiszniewski W et al (2020) Screening for genetic mutations in patients with neuropathy without definite etiology is useful. J Neurol 267:2648\u20132654. https:\/\/doi.org\/10.1007\/s00415-020-09899-w","journal-title":"J Neurol"},{"key":"6859_CR8","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1002\/mus.26348","volume":"59","author":"K Samuelsson","year":"2019","unstructured":"Samuelsson K, Radovic A, Press R et al (2019) Screening for Fabry disease and Hereditary ATTR amyloidosis in idiopathic small-fiber and mixed neuropathy. 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