Instituto de Investigação e Inovação Em Saúde (i3S), University of Porto, Porto, Portugal.
Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
J Neurol. 2024 Sep;271(9):5746-5761. doi: 10.1007/s00415-024-12509-8. Epub 2024 Jun 22.
Hereditary transthyretin-related amyloidosis (ATTRv amyloidosis) is a rare and progressively debilitating disease characterized by the deposition of transthyretin (TTR) amyloid fibrils in various organs and tissues, most commonly in the heart and peripheral nerves. This pathological deposition can lead to significant organ dysfunction and, ultimately, organ failure. ATTRv amyloidosis exhibits a broad range of clinical presentations, from purely neurological symptoms to purely cardiac manifestations, as well as mixed phenotypes which result from both neurological and cardiac implications. This wide phenotypical spectrum realistically challenges disease diagnosis and prognosis, especially in individuals without or with an unknown family history. Multiple factors are thought to contribute to this variability, including genetic, epigenetic, and even environmental influences. Understanding these factors is crucial, as they can significantly affect disease expression and progression. This review aims to summarize each of these contributing factors, to help elucidate the current knowledge on the phenotypical variability of ATTRv amyloidosis.
遗传性转甲状腺素蛋白相关淀粉样变性病（ATTRv 淀粉样变性病）是一种罕见且进行性衰弱的疾病，其特征是转甲状腺素蛋白（TTR）淀粉样纤维在各种器官和组织中的沉积，最常见于心脏和周围神经。这种病理性沉积可导致重要器官功能障碍，并最终导致器官衰竭。ATTRv 淀粉样变性病表现出广泛的临床表现，从纯粹的神经症状到纯粹的心脏表现，以及由神经和心脏影响共同导致的混合表型。这种广泛的表型谱实际上对疾病的诊断和预后构成了挑战，尤其是在没有家族史或家族史未知的个体中。多种因素被认为促成了这种变异性，包括遗传、表观遗传，甚至环境影响。了解这些因素至关重要，因为它们会显著影响疾病的表现和进展。本综述旨在总结这些促成因素，以帮助阐明目前对 ATTRv 淀粉样变性病表型变异性的认识。
