Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding ...Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils(i.e. amyloid). Apart from the common Val30 Met mutation there is a very heterogeneous group of non-Val30 Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122 del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. Results: Three patients needed a staged(1 patient) or simultaneous(2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac(allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. Conclusions: This is the first report in(liver) transplant literature about the rare Val122 del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.展开更多
目的分析Ser77Tyr突变所致转甲状腺素蛋白淀粉样变性多发性神经病(ATTR-PN)的临床特征。方法回顾性分析福建医科大学附属闽东医院神经内科收治的1例Ser77Tyr突变所致ATTR-PN患者的临床资料。检索并筛选Pubmed、Web of Science数据库及...目的分析Ser77Tyr突变所致转甲状腺素蛋白淀粉样变性多发性神经病(ATTR-PN)的临床特征。方法回顾性分析福建医科大学附属闽东医院神经内科收治的1例Ser77Tyr突变所致ATTR-PN患者的临床资料。检索并筛选Pubmed、Web of Science数据库及中国知网、万方数据库中关于Ser77Tyr突变所致ATTR-PN患者以及Pubmed、Web of Science数据库中关于Val30Met突变所致ATTR-PN患者的文献,提取患者的临床特征,汇总后比较Ser77Tyr、Val30Met突变所致ATTR-PN患者临床特征的差异。结果(1)收治患者的转甲状腺素蛋白(TTR)基因Sanger测序结果显示Ser77Tyr杂合致病性突变,刚果红染色患者发病2.5年时的胃窦活检标本显示淀粉样物质沉积。(2)最终汇总78例Ser77Tyr突变所致ATTR-PN患者,其多于50~60岁发病;男性发病率高(74.4%);多有阳性家族史(78.0%);首发症状以感觉障碍症状最常见(72.0%),数年内发展到周围神经广泛受累,同时合并普遍的心脏损害(96.4%);神经电生理检查示以轴索损害和腕管综合征表现为主;组织活检阳性率高(84.8%)。(3)汇总早发型、晚发型Val30Met突变所致ATTR-PN患者192例、96例。Ser77Tyr突变所致ATTR-PN患者深感觉障碍发生率(58.5%)高于早发型Val30Met突变所致ATTR-PN患者(28.6%),差异有统计学意义(P<0.05)。与晚发型Val30Met突变所致ATTR-PN患者比较,Ser77Tyr突变所致ATTR-PN患者浅感觉障碍发生率增高(56.3%vs.75.0%),肢体无力发生率降低(65.6%vs.48.3%),差异均有统计学意义(P<0.05)。Ser77Tyr突变所致ATTR-PN患者腕管综合征发生率(75.4%)高于早发型、晚发型Val30Met突变所致ATTR-PN患者(10.8%、25.0%),心脏损害发生率(96.4%)高于早发型Val30Met突变所致ATTR-PN患者(80.5%),差异均有统计学意义(P<0.05)。结论Ser77Tyr突变所致ATTR-PN患者具有一些相对独特的临床特征:大小纤维损害相对均衡、腕管综合征突出、心脏病变明显等,及早识别这些特征并完善活检和基因检测,有助于早期诊断。展开更多
文摘Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils(i.e. amyloid). Apart from the common Val30 Met mutation there is a very heterogeneous group of non-Val30 Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122 del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. Results: Three patients needed a staged(1 patient) or simultaneous(2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac(allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. Conclusions: This is the first report in(liver) transplant literature about the rare Val122 del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.
文摘目的分析Ser77Tyr突变所致转甲状腺素蛋白淀粉样变性多发性神经病(ATTR-PN)的临床特征。方法回顾性分析福建医科大学附属闽东医院神经内科收治的1例Ser77Tyr突变所致ATTR-PN患者的临床资料。检索并筛选Pubmed、Web of Science数据库及中国知网、万方数据库中关于Ser77Tyr突变所致ATTR-PN患者以及Pubmed、Web of Science数据库中关于Val30Met突变所致ATTR-PN患者的文献,提取患者的临床特征,汇总后比较Ser77Tyr、Val30Met突变所致ATTR-PN患者临床特征的差异。结果(1)收治患者的转甲状腺素蛋白(TTR)基因Sanger测序结果显示Ser77Tyr杂合致病性突变,刚果红染色患者发病2.5年时的胃窦活检标本显示淀粉样物质沉积。(2)最终汇总78例Ser77Tyr突变所致ATTR-PN患者,其多于50~60岁发病;男性发病率高(74.4%);多有阳性家族史(78.0%);首发症状以感觉障碍症状最常见(72.0%),数年内发展到周围神经广泛受累,同时合并普遍的心脏损害(96.4%);神经电生理检查示以轴索损害和腕管综合征表现为主;组织活检阳性率高(84.8%)。(3)汇总早发型、晚发型Val30Met突变所致ATTR-PN患者192例、96例。Ser77Tyr突变所致ATTR-PN患者深感觉障碍发生率(58.5%)高于早发型Val30Met突变所致ATTR-PN患者(28.6%),差异有统计学意义(P<0.05)。与晚发型Val30Met突变所致ATTR-PN患者比较,Ser77Tyr突变所致ATTR-PN患者浅感觉障碍发生率增高(56.3%vs.75.0%),肢体无力发生率降低(65.6%vs.48.3%),差异均有统计学意义(P<0.05)。Ser77Tyr突变所致ATTR-PN患者腕管综合征发生率(75.4%)高于早发型、晚发型Val30Met突变所致ATTR-PN患者(10.8%、25.0%),心脏损害发生率(96.4%)高于早发型Val30Met突变所致ATTR-PN患者(80.5%),差异均有统计学意义(P<0.05)。结论Ser77Tyr突变所致ATTR-PN患者具有一些相对独特的临床特征:大小纤维损害相对均衡、腕管综合征突出、心脏病变明显等,及早识别这些特征并完善活检和基因检测,有助于早期诊断。
