Baseline disease characteristics in Brazilian patients enrolled in Transthyretin Amyloidosis Outcome Survey (THAOS)

ABSTRACT Transthyretin amyloidosis (ATTR) is characterized by the deposit of mutant or wild-type transthyretin that forms amyloid fibrils, which are extracellularly deposited within tissues and organs. Clinical manifestations of familial amyloid polyneuropathy vary according to the mutation, age at onset and geographical location. This study aimed to describe baseline disease characteristics of Brazilian patients with transthyretin familial amyloid polyneuropathy (ATTR-FAP) enrolled in the Transthyretin Amyloidosis Outcome Survey (THAOS). Methods: The THAOS is an international, noninterventional, longitudinal, observational, web-based registry designed to characterize ATTR. The outcome measures included demographics (age at symptom onset, gender, time from onset of symptoms to diagnosis, family history), genotype, and clinical characteristics (presence of amyloid deposit, frequency of misdiagnosis, presenting symptomatology). The analysis was conducted in a dataset from Brazilian patients (from November 2008 to January 2016). Results: One hundred and sixty participants (52.5% male) were included in the analysis. The majority of participants (90.6%) reported a positive family history of ATTR-FAP Median age at symptom onset was 32.5 years. Val30Met mutation was found in 91.9%. Misdiagnosis was observed in 26.6% of symptomatic patients. Over one-third (35.3%) of the misdiagnosed patients experienced a delay of more than one year before receiving a correct diagnosis. At presentation, 79.7% of the patients had motor, 87.5% sensory and 93.8% autonomic symptoms. Conclusion: ATTR-FAP in Brazil starts early, has a strong family history and the majority has Val30Met mutation. Misdiagnosis is common and the most common presentation is of a sensorimotor and autonomic neuropathy.

摘要 转甲状腺素蛋白淀粉样变性（Transthyretin Amyloidosis, ATTR）以突变型或野生型转甲状腺素蛋白沉积形成淀粉样纤维为特征，此类纤维可在组织与器官内细胞外沉积。家族性淀粉样多发性神经病（Familial Amyloid Polyneuropathy, FAP）的临床表现因突变类型、发病年龄及地理位置而异。本研究旨在描述纳入转甲状腺素蛋白淀粉样变性结局调查（Transthyretin Amyloidosis Outcome Survey, THAOS）的巴西转甲状腺素蛋白家族性淀粉样多发性神经病（ATTR-FAP）患者的基线疾病特征。

方法：THAOS是一项国际性、非干预性、纵向观察性网络注册研究，旨在表征ATTR的疾病特征。其结局指标包括人口统计学资料（症状发作年龄、性别、从症状发作至确诊的时间、家族史）、基因型，以及临床特征（淀粉样蛋白沉积情况、误诊发生率、首发症状）。本次分析基于2008年11月至2016年1月期间的巴西患者数据集完成。

结果：本研究共纳入160名参与者（52.5%为男性）。绝大多数参与者（90.6%）报告存在ATTR-FAP阳性家族史。症状发作中位年龄为32.5岁。91.9%的患者检出Val30Met突变。26.6%的有症状患者存在误诊情况。超过三分之一（35.3%）的误诊患者在获得正确诊断前延误时长超过1年。就诊时，79.7%的患者存在运动症状，87.5%存在感觉症状，93.8%存在自主神经症状。

结论：巴西人群中的ATTR-FAP发病年龄较早，家族史阳性率较高，且绝大多数患者携带Val30Met突变。误诊情况较为常见，最常见的临床表现为感觉运动性与自主神经病变。