Chen Hong-Tao, Tian You-Jun, Zhang Jue, Xiao Bing-Rong, Yang Ke, Zhang Ya-Li
Department of Diagnostic Imaging Center, First People's Hospital of Tianmen, Jingling people Avenue East No. 1, Tianmen City, 431701, Hubei Province, China.
Orphanet J Rare Dis. 2025 May 5;20(1):213. doi: 10.1186/s13023-025-03736-x.
This study aimed to characterize the clinical and neuroimaging features of hereditary leptomeningeal transthyretin amyloidosis (hATTR-LA), a dominant inheritance disorder caused by a heterozygous TTR gene mutation.
A comprehensive retrospective evaluation was conducted, incorporating detailed clinical records, multimodal neuroimaging findings, and a systematic review of the literature to contextualize the observations.
The patient was a 55-year-old male who presented with chronic central nervous system symptoms, including sensory-motor peripheral neuropathy and progressive visual impairment. Cerebrospinal fluid analysis revealed elevated protein levels. Neuroimaging showed progressive leptomeningeal hyperdensity on CT and characteristic linear thickening with enhancement of the leptomeninges on MRI, involving both cerebral and spinal regions. Genetic testing confirmed the diagnosis by identifying a heterozygous c.265T > C (p.Y89H) pathogenic variant in exon 3 of the TTR gene, classified as pathogenic according to ACMG guidelines.
Multimodal imaging provides valuable, non-invasive insights for diagnosing hATTR-LA, enhancing diagnostic accuracy and informing clinical management of this rare condition.
本研究旨在描述遗传性软脑膜转甲状腺素蛋白淀粉样变性（hATTR-LA）的临床和神经影像学特征，这是一种由杂合型TTR基因突变引起的显性遗传疾病。
进行了全面的回顾性评估，纳入详细的临床记录、多模态神经影像学检查结果，并对文献进行系统回顾，以将观察结果置于背景中。
患者为一名55岁男性，表现为慢性中枢神经系统症状，包括感觉运动性周围神经病和进行性视力损害。脑脊液分析显示蛋白水平升高。神经影像学检查显示，CT上软脑膜密度逐渐增高，MRI上软脑膜呈特征性线性增厚并强化，累及脑和脊髓区域。基因检测通过在TTR基因第3外显子中鉴定出一个杂合型c.265T＞C（p.Y89H）致病变异确诊，根据美国医学遗传学与基因组学学会（ACMG）指南，该变异被分类为致病变异。
多模态成像为hATTR-LA的诊断提供了有价值的非侵入性见解，提高了诊断准确性，并为这种罕见疾病的临床管理提供了信息。
