Prevalence of hereditary transthyretin amyloid polyneuropathy in idiopathic progressive neuropathy in conurban areas
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(2019) 1:30
Neurological Research and Practice
RESEARCH ARTICLE
Open Access
Prevalence of hereditary transthyretin amyloid polyneuropathy in idiopathic progressive neuropathy in conurban areas Andreas Thimm1, Saskia Bolz1, Michael Fleischer1, Benjamin Stolte1, Sebastian Wurthmann1, Andreas Totzeck1, Alexander Carpinteiro5,6, Peter Luedike2,6, Maria Papathanasiou2, Christoph Rischpler3,6, Ken Herrmann3, Tienush Rassaf2, Lars Steinmüller-Magin4, Christoph Kleinschnitz1 and Tim Hagenacker1,6*
Abstract Background: Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a rare, genetically heterogenous, and clinically variable autosomal dominant disease that severely reduces life expectancy. As treatment options grow, a proper diagnostic approach is mandatory especially in non-endemic regions with diverse genetic backgrounds. Methods: We examined 102 neuropathy patients at a German neuromuscular centre. Common causes of polyneuropathy were ruled out by medical history and extensive laboratory testing to define a cohort of patients with progressive polyneuropathy classified as idiopathic. Molecular genetic testing of the entire TTR gene was performed, and the detected amyloidogenic and non-amyloidogenic variants were associated with the observed clinical phenotypes and results of prior diagnostic testing. Results: Two of 102 patients tested positive for amyloidogenic mutations (p.Ile127Val and p.Glu81Lys), while a variant of unknown significance, p.Glu26Ser, was found in 10 cases. In both positive cases, previous negative biopsy results were proved by gene sequencing to be false negative. In case of the p.Glu81Lys mutation we detected clinical presentation (combination of severe polyneuropathy and cardiomyopathy), ethnic background (patient of polish origin, mutation only reported in Japanese families before), and disease course clearly differed from wellknown cases of the same mutation in the literature. Conclusions: In conclusion, transthyretin hereditary amyloid polyneuropathy (ATTR-PN) should be considered in cases of otherwise idiopathic polyneuropathy. Sequencing of the four exons of the TTR gene should be considered the key step in diagnosis, while tissue biopsy possibly leads to false negative results. Keywords: TTR, Amyloidosis, Cardiomyopathy, Epidemiology, Genotype-phenotype correlation
Background Hereditary transthyretin amyloidosis is a rare, potentially life-threatening autosomal-dominant disease characterised by extracellular deposition of amyloid fibrils composed of transthyretin (TTR). TTR is a homotetrameric plasma protein transporting thyroxine and retinol binding protein-vitamin A complex [1]. It is mainly synthesised in the liver and to a far lesser extent in the * Correspondence: [email protected] 1 Department of Neurology, University Hospital Essen, Essen, Germany 6 West-German Amyloidosis NETwork, University Hospital Essen, Essen, Germany Full list of author information is available at the end of the article
choroid plexus and the retinal pigment epithelium [2]. Tetramer dissoci
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