Hereditary transthyretin amyloidosis overview
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REVIEW ARTICLE
Hereditary transthyretin amyloidosis overview Fiore Manganelli 1
&
Gian Maria Fabrizi 2 & Marco Luigetti 3,4 & Paola Mandich 5,6 & Anna Mazzeo 7 & Davide Pareyson 8
Received: 14 September 2020 / Accepted: 5 November 2020 # The Author(s) 2020
Abstract Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis is a rare autosomal dominantly inherited disorder caused by mutations in the transthyretin (TTR) gene. The pathogenetic model of ATTRv amyloidosis indicates that amyloidogenic, usually missense, mutations destabilize the native TTR favouring the dissociation of the tetramer into partially unfolded species that selfassemble into amyloid fibrils. Amyloid deposits and monomer-oligomer toxicity are the basis of multisystemic ATTRv clinical involvement. Peripheral nervous system (autonomic and somatic) and heart are the most affected sites. In the last decades, a better knowledge of pathomechanisms underlying the disease led to develop novel and promising drugs that are rapidly changing the natural history of ATTRv amyloidosis. Thus, clinicians face the challenge of timely diagnosis for addressing patients to appropriate treatment. As well, the progressive nature of ATTRv raises the issue of presymptomatic testing and risk management of carriers. The main aim of this review was to focus on what we know about ATTRv so far, from pathogenesis to clinical manifestations, diagnosis and hence patient’s monitoring and treatment, and from presymptomatic testing to management of carriers. Keywords Transthyretin . TTR . ATTRv . Amyloidosis
Introduction Hereditary amyloidogenic transthyretin (ATTRv; v for “variant”) amyloidosis is caused by mutations in the transthyretin (TTR) gene and is an autosomal dominantly inherited, debilitating, progressive and, if left untreated, fatal multisystem disorder. Prevalence of the disease is highly variable between
the endemic and non-endemic countries and the global prevalence was estimated to be 10,186 persons (range 5526– 38,468) [1]. The main aim of this review is to provide an overview on ATTRv amyloidosis from pathogenesis to clinical manifestations, diagnosis and hence patient’s monitoring and treatment and from presymptomatic testing to management of carriers.
Gian Maria Fabrizi, Marco Luigetti, Paola Mandich, Anna Mazzeo and Davide Pareyson are in alphabetical order and contributed equally to this manuscript * Fiore Manganelli [email protected]; [email protected] 1
Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples “Federico II”, Via S. Pansini, 5, 80131 Naples, Italy
2
Section of Neurology, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
3
Fondazione Policlinico Universitario A. Gemelli. UOC Neurologia, Rome, Italy
4
Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy
5
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, Genova, Italy
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