Department of Amyloidosis Research, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch Machi, Sasebo City, Nagasaki, 859-3298, Japan.
Hospital Universitário Clementino Fraga Filho, Centro de Estudos em Paramiloidose Antônio Rodrigues de Mello, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Orphanet J Rare Dis. 2023 Oct 12;18(1):323. doi: 10.1186/s13023-023-02910-3.
Hereditary transthyretin (ATTRv) amyloidosis is a rare and autosomal dominant disorder associated with mutations in the transthyretin gene. Patients present with diverse symptoms related to sensory, motor, and autonomic neuropathy, as well as gastrointestinal, ocular, cardiac, renal and orthopedic symptoms, resulting from the deposition of transthyretin amyloid fibrils in multiple organs. The progressive nature of ATTRv amyloidosis necessitates pre- and post-onset monitoring of the disease. This review article is primarily based on a collation of discussions from a medical advisory board meeting in August 2021. In this article, we summarize the best practices in amyloidosis centers in three major endemic countries for ATTRv amyloidosis (Japan, Brazil, and Portugal), where most patients carry the Val30Met mutation in the transthyretin gene and the patients' genetic background was proven to be the same. The discussions highlighted the similarities and differences in the management of asymptomatic gene mutation carriers among the three countries in terms of the use of noninvasive tests and tissue biopsies and timing of starting the investigations. In addition, this article discusses a set of practical tests and examinations for monitoring disease progression applicable to neurologists working in diverse medical settings and generalizable in non-endemic countries and areas. This set of assessments consists of periodic (every 6 to 12 months) evaluations of patients' nutritional status and autonomic, renal, cardiac, ophthalmologic, and neurological functions. Physical examinations and patient-reported outcome assessments should be also scheduled every 6 to 12 months. Programs for monitoring gene mutation carriers and robust referral networks can aid in appropriate patient management in pre- to post-onset stages. For pre- and post-symptom onset testing for ATTRv amyloidosis, various noninvasive techniques are available; however, their applicability differs depending on the medical setting in each country and region, and the optimal option should be selected in view of the clinical settings, medical environment, and available healthcare resources in each region.
遗传性转甲状腺素蛋白（ATTR）淀粉样变是一种罕见的常染色体显性遗传疾病，与转甲状腺素蛋白基因的突变有关。患者表现出多种症状，包括感觉、运动和自主神经病，以及胃肠道、眼部、心脏、肾脏和骨科症状，这些症状是由转甲状腺素蛋白淀粉样纤维在多个器官中的沉积引起的。ATTR 淀粉样变的进行性特征需要对疾病进行发病前和发病后的监测。本文主要基于 2021 年 8 月医学顾问委员会会议的讨论内容。本文总结了三个ATTR 淀粉样变主要流行国家（日本、巴西和葡萄牙）的淀粉样变中心的最佳实践，这些国家的大多数患者携带转甲状腺素蛋白基因中的 Val30Met 突变，且患者的遗传背景被证明是相同的。讨论强调了这三个国家在无症状基因突变携带者的管理方面的相似之处和差异，包括非侵入性检测和组织活检的使用以及开始这些检查的时间。此外，本文还讨论了一套适用于在不同医疗环境中工作的神经科医生监测疾病进展的实用检测和检查方法，这些方法在非流行国家和地区也具有可推广性。这组评估包括定期（每 6 至 12 个月）评估患者的营养状况以及自主、肾脏、心脏、眼科和神经功能。还应每 6 至 12 个月安排一次体检和患者报告的结果评估。基因突变携带者监测计划和强大的转诊网络可以帮助在发病前至发病后阶段进行适当的患者管理。对于 ATTRv 淀粉样变的发病前和发病后检测，有多种非侵入性技术可用；然而，它们的适用性因每个国家和地区的医疗环境而异，应根据每个地区的临床环境、医疗环境和可用的医疗保健资源选择最佳方案。
