遗传性转甲状腺素蛋白介导的淀粉样变性(hATTR)由于临床表现的异质性,早期诊断具有挑战性。根据TTR基因变体及其在每个个体中的外显率而不同。在英国和爱尔兰最常见的TTR变体(T80A,V142I和V50M)与其他地理位置常见的情况不同,因此需要对诊断和基因测试进行具体考虑。此外,最近这种情况的治疗方法加强了对患者管理的更一致方法的需求,包括获得专业服务,基因检测和咨询,以及居住在英国和爱尔兰的家庭的临床调查。召集了来自英国和爱尔兰的多学科专家小组,以确定当前的挑战,提供建议,并为诊断和筛查患者达成共识,或者有风险,HATTR.在一系列会议上,专家们分享了他们目前的做法并起草了,完善并批准了一份共识声明。该共识声明为三个不同组提供了建议:(1)有症状的人增加了hATTR淀粉样变性的可能性;(2)活检证实hATTR淀粉样变性的人;(3)没有症状的人可能患有hATTR淀粉样变性(即具有确定的TTR变体的人的亲属)。对于每个小组,建议对有症状的患者进行诊断和随访所需的步骤,以及为有风险个体的咨询和症状前基因检测提供专家支持的指导。本指南旨在实用并基于现有证据。目的是让区域淀粉样蛋白专科中心及时提供诊断,临床筛查,以及对患有hATTR淀粉样变性的个体及其家庭的治疗。
Hereditary transthyretin-mediated amyloidosis (hATTR) is challenging to diagnose early owing to the heterogeneity of clinical presentation, which differs according to the TTR gene variant and its penetrance in each individual. The TTR variants seen most frequently in the UK and Ireland (T80A, V142I and V50M) differ to those commonly occurring in other geographic locations and warrant a specific consideration for diagnosis and genetic testing. In addition, recent availability of treatment for this condition has reinforced the need for a more consistent approach to the management of patients, including access to specialist services, genetic testing and counselling, and clinical investigation for families living in the UK and Ireland. A multidisciplinary panel of experts from the UK and Ireland was convened to identify the current challenges, provide recommendations, and develop a
consensus for the diagnosis and screening of people with, or at risk of, hATTR. Over a series of meetings, experts shared their current practices and drafted, refined and approved a
consensus statement. This
consensus statement provides recommendations for three different groups: (1) people with symptoms raising a possibility of hATTR amyloidosis; (2) people with biopsy-confirmed hATTR amyloidosis; and (3) people without symptoms who may have hATTR amyloidosis (i.e. relatives of people with identified TTR variants). For each group, recommendations are made for the required steps for the diagnosis and follow-up of symptomatic patients, and for guidance on the specialist support for counselling and pre-symptomatic genetic testing of at-risk individuals. This guidance is intended to be practical and based on available evidence. The aim is for regional amyloid specialist centres to provide timely diagnosis, clinical screening, and treatment for individuals and their families with hATTR amyloidosis.