Ellen & Martin Prosserman Centre for Neuromuscular Diseases, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Division of Neurology, Department of Medicine, The University of British Columbia, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Can J Neurol Sci. 2022 Jan;49(1):7-18. doi: 10.1017/cjn.2021.34. Epub 2021 Feb 26.
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.
遗传性转甲状腺素蛋白介导的（hATTR）淀粉样变是一种由 TTR 基因突变引起的进行性疾病，可导致多系统器官功能障碍。致病性 TTR 聚集、错误折叠和纤维形成导致淀粉样物质在多个身体器官中沉积，并经常涉及周围神经系统和心脏。常见的神经表现包括：感觉运动性多发性神经病（PN）、自主神经病、小纤维 PN 和腕管综合征。由于 hATTR PN 不在鉴别诊断范围内，因此许多患者由于诊断延迟而导致病情显著进展。最近，两种有效的新型疾病修饰疗法，即 inotersen 和 patisiran，已获得加拿大卫生部批准用于治疗 hATTR PN。早期诊断对于及时引入这些疾病修饰治疗至关重要，这些治疗可以减少损伤、提高生活质量并延长生存期。在本指南中，我们旨在通过针对加拿大的诊断、监测和治疗提出建议来提高对 hATTR PN 的认识并改善其结局。
