Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples "Federico II", Via S. Pansini, 5, 80131, Naples, Italy.
Section of Neurology, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Neurol Sci. 2022 Dec;43(Suppl 2):595-604. doi: 10.1007/s10072-020-04889-2. Epub 2020 Nov 14.
Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis is a rare autosomal dominantly inherited disorder caused by mutations in the transthyretin (TTR) gene. The pathogenetic model of ATTRv amyloidosis indicates that amyloidogenic, usually missense, mutations destabilize the native TTR favouring the dissociation of the tetramer into partially unfolded species that self-assemble into amyloid fibrils. Amyloid deposits and monomer-oligomer toxicity are the basis of multisystemic ATTRv clinical involvement. Peripheral nervous system (autonomic and somatic) and heart are the most affected sites. In the last decades, a better knowledge of pathomechanisms underlying the disease led to develop novel and promising drugs that are rapidly changing the natural history of ATTRv amyloidosis. Thus, clinicians face the challenge of timely diagnosis for addressing patients to appropriate treatment. As well, the progressive nature of ATTRv raises the issue of presymptomatic testing and risk management of carriers. The main aim of this review was to focus on what we know about ATTRv so far, from pathogenesis to clinical manifestations, diagnosis and hence patient's monitoring and treatment, and from presymptomatic testing to management of carriers.
遗传性转甲状腺素蛋白淀粉样变（ATTRv）是一种罕见的常染色体显性遗传性疾病，由转甲状腺素蛋白（TTR）基因的突变引起。ATTRv 淀粉样变的发病机制模型表明，淀粉样变性的，通常是错义，突变会使天然 TTR 不稳定，有利于四聚体解离成部分展开的物种，这些物种会自我组装成淀粉样纤维。淀粉样沉积物和单体-寡聚物毒性是 ATTRv 多系统临床受累的基础。周围神经系统（自主和躯体）和心脏是最受影响的部位。在过去的几十年中，对疾病发病机制的更好了解导致了新型有前途的药物的开发，这些药物正在迅速改变 ATTRv 淀粉样变的自然病史。因此，临床医生面临着及时诊断的挑战，以便为患者提供适当的治疗。此外，ATTRv 的进行性特征提出了对携带者进行无症状检测和风险管理的问题。本综述的主要目的是聚焦于迄今为止我们对 ATTRv 的了解，从发病机制到临床表现、诊断，进而到患者的监测和治疗，以及从无症状检测到携带者的管理。
