BACKGROUND: Transthyretin (TTR) amyloidosis is a rare, life-threatening, systemic, autosomal dominant condition occurring in adults, with two main forms: hereditary (associated with TTR gene mutations) and wild-type. Studies indicate considerable heterogeneity in disease presentation, with predominantly polyneuropathic, predominantly cardiac, or mixed phenotypes. METHODS: THAOS - the Transthyretin Amyloidosis Outcomes Survey - is the first global, multicenter, longitudinal, observational survey that collects data on the natural history of TTR amyloidosis (ClinicalTrials.gov: NCT00628745). This paper presents data on signs and symptoms, neurological and cardiac assessments, biomarkers and quality of life in the patients enrolled in THAOS from its inception in December 2007 to September 2011. RESULTS: At the time of this analysis, data were available from 611 symptomatic patients with hereditary TTR amyloidosis, 67 symptomatic patients with wild-type TTR amyloidosis, and 274 currently asymptomatic individuals with a TTR mutation. Nineteen countries were participating in the registry. The largest patient groups came from Portugal (n = 453), the USA (n = 129), Italy (n = 70), and Japan (n = 68). Predominant symptom presentation in patients with hereditary TTR amyloidosis differed according to the underlying disease-causing mutation (polyneuropathy for Val30Met, cardiomyopathy for Val122Ile and Leu111Met, and mixed for Glu89Gln). However, each mutation was associated with clear multisystem involvement. Similarly, although cardiomyopathy was predominant in patients with wild-type TTR amyloidosis, many also showed symptoms consistent with neuropathy. Quality of life in patients with hereditary TTR amyloidosis, but not asymptomatic carriers of disease-causing mutations, was severely impaired relative to that of the age-matched general US population. CONCLUSIONS: This preliminary analysis highlights the considerable phenotypic heterogeneity for neurological and cardiac manifestations in patients with hereditary and wild-type TTR amyloidosis and the necessity of providing multidisciplinary care. THAOS registry data will help better characterize the diverse presentation and course of TTR amyloidosis worldwide and aid in improving and standardizing diagnosis and treatment.
BACKGROUND:Transthyretin (TTR) amyloidosis is a rare, life-threatening, systemic, autosomal dominant condition occurring in adults, with two main forms: hereditary (associated with TTR gene mutations) and wild-type. Studies indicate considerable heterogeneity in disease presentation, with predominantly polyneuropathic, predominantly cardiac, or mixed phenotypes. METHODS: THAOS - the Transthyretin Amyloidosis Outcomes Survey - is the first global, multicenter, longitudinal, observational survey that collects data on the natural history of TTRamyloidosis (ClinicalTrials.gov: NCT00628745). This paper presents data on signs and symptoms, neurological and cardiac assessments, biomarkers and quality of life in the patients enrolled in THAOS from its inception in December 2007 to September 2011. RESULTS: At the time of this analysis, data were available from 611 symptomatic patients with hereditary TTR amyloidosis, 67 symptomatic patients with wild-type TTRamyloidosis, and 274 currently asymptomatic individuals with a TTR mutation. Nineteen countries were participating in the registry. The largest patient groups came from Portugal (n = 453), the USA (n = 129), Italy (n = 70), and Japan (n = 68). Predominant symptom presentation in patients with hereditary TTR amyloidosis differed according to the underlying disease-causing mutation (polyneuropathy for Val30Met, cardiomyopathy for Val122Ile and Leu111Met, and mixed for Glu89Gln). However, each mutation was associated with clear multisystem involvement. Similarly, although cardiomyopathy was predominant in patients with wild-type TTRamyloidosis, many also showed symptoms consistent with neuropathy. Quality of life in patients with hereditary TTR amyloidosis, but not asymptomatic carriers of disease-causing mutations, was severely impaired relative to that of the age-matched general US population. CONCLUSIONS: This preliminary analysis highlights the considerable phenotypic heterogeneity for neurological and cardiac manifestations in patients with hereditary and wild-type TTRamyloidosis and the necessity of providing multidisciplinary care. THAOS registry data will help better characterize the diverse presentation and course of TTRamyloidosis worldwide and aid in improving and standardizing diagnosis and treatment.
Authors: Peter J Dyck; John C Kincaid; P James B Dyck; Vinay Chaudhry; Namita A Goyal; Christina Alves; Hayet Salhi; Janice F Wiesman; Celine Labeyrie; Jessica Robinson-Papp; Márcio Cardoso; Matilde Laura; Katherine Ruzhansky; Andrea Cortese; Thomas H Brannagan; Julie Khoury; Sami Khella; Márcia Waddington-Cruz; João Ferreira; Annabel K Wang; Marcus V Pinto; Samar S Ayache; Merrill D Benson; John L Berk; Teresa Coelho; Michael Polydefkis; Peter Gorevic; David H Adams; Violaine Plante-Bordeneuve; Carol Whelan; Giampaolo Merlini; Stephen Heitner; Brian M Drachman; Isabel Conceição; Christopher J Klein; Morie A Gertz; Elizabeth J Ackermann; Steven G Hughes; Michelle L Mauermann; Rito Bergemann; Karen A Lodermeier; Jenny L Davies; Rickey E Carter; William J Litchy Journal: Muscle Nerve Date: 2017-04-07 Impact factor: 3.217
Authors: Kayalvizhi Madhivanan; Erin R Greiner; Miguel Alves-Ferreira; David Soriano-Castell; Nirvan Rouzbeh; Carlos A Aguirre; Johan F Paulsson; Justin Chapman; Xin Jiang; Felicia K Ooi; Carolina Lemos; Andrew Dillin; Veena Prahlad; Jeffery W Kelly; Sandra E Encalada Journal: Proc Natl Acad Sci U S A Date: 2018-07-30 Impact factor: 11.205
Authors: M Ankarcrona; B Winblad; C Monteiro; C Fearns; E T Powers; J Johansson; G T Westermark; J Presto; B-G Ericzon; J W Kelly Journal: J Intern Med Date: 2016-05-10 Impact factor: 8.989
Authors: Keyur B Shah; Anit K Mankad; Adam Castano; Olakunle O Akinboboye; Phillip B Duncan; Icilma V Fergus; Mathew S Maurer Journal: Circ Heart Fail Date: 2016-06 Impact factor: 8.790