Lysholm Department of Neuroradiology, National Hospital for Neurology & Neurosurgery, Queen Square, London, UK.
Department of Neurology, Frimley Park Hospital, Surrey, UK.
J Neurol Sci. 2024 Nov 15;466:123273. doi: 10.1016/j.jns.2024.123273. Epub 2024 Oct 15.
This case report aims to contribute to the expanding genotypic-phenotypic spectrum of TTR associated leptomeningeal amyloidosis.
Neuroimaging and targeted TTR Sanger sequencing were performed on a 52-year-old female presenting with cognitive and motor symptoms.
The proband, a Sri Lankan woman, presented with a gradually progressive cognitive decline, followed by a rapid deterioration in motor function and level of consciousness. She had a significant family history of an undiagnosed neurological disorder, characterized by cognitive impairment and early death occurring in the fifth decade of life. Analysis of cerebrospinal fluid (CSF) demonstrated elevated protein levels. CT scan of the brain showed extensive leptomeningeal calcifications and hydrocephalus, and gadolinium enhanced magnetic resonance imaging (MRI) demonstrated extensive leptomeningeal enhancement in the brain and spinal cord. Genetic analysis revealed c.113 A > G, p.D38G mutation in TTR, a rare mutation with characteristic clinic-radiological central nervous system features.
Leptomeningeal amyloidosis represents the least common subtype of familial transthyretin amyloidosis, which is a life-threatening condition. Among the over 150 identified mutations, few are specifically associated with central nervous system disease. The genetic spectrum and clinical phenotypes including neuroimaging findings continue to expand. It is important to maintain a high index of suspicion for leptomeningeal amyloidosis, particularly when the presentation is not acute or when there are relapsing-remitting symptoms. Consideration of family history and early genetic testing are essential to facilitate appropriate treatment and genetic counselling.
本病例报告旨在丰富转甲状腺素蛋白相关脑脊髓液淀粉样变病的基因型-表型谱。
对一名 52 岁出现认知和运动症状的女性进行神经影像学和靶向转甲状腺素蛋白 Sanger 测序。
先证者是一名斯里兰卡女性，表现为进行性认知功能下降，随后运动功能和意识水平迅速恶化。她有一个未确诊的神经障碍家族史，其特征是认知障碍和早逝，发生在 50 岁左右。脑脊液（CSF）分析显示蛋白水平升高。脑部 CT 扫描显示广泛的软脑膜钙化和脑积水，钆增强磁共振成像（MRI）显示大脑和脊髓广泛的软脑膜增强。基因分析显示 TTR 中的 c.113A>G，p.D38G 突变，这是一种罕见的突变，具有特征性的临床放射学中枢神经系统表现。
脑脊髓液淀粉样变病是家族性转甲状腺素蛋白淀粉样变病中最不常见的亚型，是一种危及生命的疾病。在已鉴定的 150 多种突变中，很少有突变与中枢神经系统疾病有明确的相关性。遗传谱和临床表型，包括神经影像学发现，不断扩大。当表现不呈急性或出现缓解-复发症状时，应高度怀疑脑脊髓液淀粉样变病，这一点非常重要。考虑家族史和早期基因检测对于提供适当的治疗和遗传咨询至关重要。
