THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis
THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis
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DOI：
10.1185/03007995.2012.754348
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发表时间：
2013-01-01
影响因子：
2.3
通讯作者：
Suhr, Ole B.
中科院分区：
文献类型：
--
作者：
Coelho, Teresa;Maurer, Mathew S.;Suhr, Ole B.
背景：甲状腺素运载蛋白（TTR）淀粉样变性是一种罕见的，危及生命的，全身性，常染色体显性疾病发生在成人，有两种主要形式：遗传性（与TTR基因突变相关）和野生型。研究表明，相当大的异质性疾病presentation.Methods的，主要是多神经病变，主要是心脏，或混合phenotypes. THAOS -甲状腺素运载蛋白淀粉样变性结局调查-是第一个全球性的，多中心的，纵向的，观察性调查，收集数据的TTR淀粉样变性的自然史（ClinicalTrials.gov：NCT 00628745）。本文介绍了THAOS自2007年12月成立至2011年9月招募的患者的体征和症状、神经和心脏评估、生物标志物和生活质量的数据。结果：在本分析时，可获得611例有症状的遗传性TTR淀粉样变性患者、67例有症状的野生型TTR淀粉样变性患者和274例目前无症状的TTR突变个体的数据。19个国家参加了登记册。最大的患者组来自葡萄牙（n = 453）、美国（n = 129）、意大利（n = 70）和日本（n = 68）。遗传性TTR淀粉样变性患者的主要症状表现根据潜在的致病突变而不同（Val 30 Met为多发性神经病，Val 122 Ile和Leu 111 Met为心肌病，Glu 89 Gln为混合型）。然而，每个突变都与明确的多系统参与有关。类似地，尽管心肌病在野生型TTR淀粉样变性患者中占主导地位，但许多患者也表现出与神经病变一致的症状。遗传性TTR淀粉样变性患者的生活质量，但不是无症状的致病突变的载体，是严重受损相对于年龄匹配的一般USpopulation.Conclusions：这个初步分析突出了相当大的表型异质性神经和心脏表现的遗传性和野生型TTR淀粉样变性患者和提供多学科护理的必要性。THAOS登记数据将有助于更好地描述全球TTR淀粉样变性的不同表现和病程，并有助于改善和标准化诊断和治疗。
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.