Poli Loris, Labella Beatrice, Cotti Piccinelli Stefano, Caria Filomena, Risi Barbara, Damioli Simona, Padovani Alessandro, Filosto Massimiliano
Unit of Neurology, Azienda Socio-Sanitaria Territoriale Spedali Civili, Brescia, Italy.
Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Front Neurol. 2023 Oct 5;14:1242815. doi: 10.3389/fneur.2023.1242815. eCollection 2023.
Amyloidoses represent a group of diseases characterized by the pathological accumulation in the extracellular area of insoluble misfolded protein material called "amyloid". The damage to the tissue organization and the direct toxicity of the amyloidogenic substrates induce progressive dysfunctions in the organs involved. They are usually multisystem diseases involving several vital organs, such as the peripheral nerves, heart, kidneys, gastrointestinal tract, liver, skin, and eyes. Transthyretin amyloidosis (ATTR) is related to abnormalities of transthyretin (TTR), a protein that acts as a transporter of thyroxine and retinol and is produced predominantly in the liver. ATTR is classified as hereditary (ATTRv) and wild type (ATTRwt). ATTRv is a severe systemic disease of adults caused by mutations in the gene and transmitted in an autosomal dominant manner with incomplete penetrance. Some pathogenic variants in are preferentially associated with a neurological phenotype (progressive peripheral sensorimotor polyneuropathy); others are more frequently associated with restrictive heart failure. However, many mutations express a mixed phenotype with neurological and cardiological involvement. ATTRv is now a treatable disease. A timely and definite diagnosis is essential in view of the availability of effective therapies that have revolutionized the management of affected patients. The purpose of this review is to familiarize the clinician with the disease and with the correct diagnostic pathways in order to obtain an early diagnosis and, consequently, the possibility of an adequate treatment.
淀粉样变性是一类疾病，其特征是在细胞外区域病理性积聚一种称为“淀粉样蛋白”的不溶性错误折叠蛋白质物质。对组织结构的损害以及淀粉样蛋白生成底物的直接毒性会导致受累器官逐渐出现功能障碍。它们通常是多系统疾病，累及多个重要器官，如周围神经、心脏、肾脏、胃肠道、肝脏、皮肤和眼睛。转甲状腺素蛋白淀粉样变性（ATTR）与转甲状腺素蛋白（TTR）异常有关，TTR是一种作为甲状腺素和视黄醇转运蛋白的蛋白质，主要在肝脏中产生。ATTR分为遗传性（ATTRv）和野生型（ATTRwt）。ATTRv是一种由该基因突变引起的成人严重全身性疾病，以常染色体显性方式遗传，外显率不完全。该基因中的一些致病变体优先与神经表型（进行性周围感觉运动性多发性神经病）相关；其他变体则更常与限制性心力衰竭相关。然而，许多突变表现出神经和心脏受累的混合表型。ATTRv现在是一种可治疗的疾病。鉴于有效疗法的出现彻底改变了对受影响患者的管理，及时明确的诊断至关重要。本综述的目的是使临床医生熟悉该疾病以及正确的诊断途径，以便获得早期诊断，从而有可能进行充分治疗。
