Niemann-Pick disease type C1 predominantly involving the frontotemporal region, with cortical and brainstem Lewy bodies: An autopsy case
Niemann-Pick disease type C1 predominantly involving the frontotemporal region, with cortical and brainstem Lewy bodies: An autopsy case
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DOI：
10.1111/neup.12047
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发表时间：
2014-02-01
期刊：
影响因子：
2.3
通讯作者：
Shimada, Atsuyoshi
中科院分区：
文献类型：
--
作者：
Chiba, Yoichi;Komori, Hiraku;Shimada, Atsuyoshi
C型尼曼-匹克病（NPC）是一种常染色体隐性遗传的神经内脏脂质沉积症。目前已发现两个致病基因（NPC 1和NPC 2）。NPC的特征在于神经元和神经胶质细胞的脂质储存和NFT。在这里，我们报告一名男子与青少年发病进行性神经功能缺损，包括锥体束征，共济失调，球麻痹，垂直核上性眼肌麻痹，精神症状，死亡发生在37岁之前明确的临床诊断。尸检发现脑萎缩的独特分布，主要是在额叶和颞叶。显微镜下，观察到神经元中的脂质储存和广泛分布的NFT。脂肪储存细胞出现在全身器官和菲律宾染色表明细胞内胆固醇积累在肝巨噬细胞。电子显微镜显示脂质和特征性寡层包涵体的积累。这些结果提示NPC诊断。神经元丢失和神经胶质增生经常伴有NFT，发生在额叶和颞叶皮质、海马、杏仁核、基底前脑、基底神经节、丘脑、黑质和脑干核。路易体（LB）中观察到的大多数，但不是所有的区域，NFT是明显的。相比之下，神经元脂质储存发生在更广泛的区域，包括顶叶和枕叶皮质，其中NFT或LB的神经变性最小。分子遗传学分析表明，患者在NPC 1基因的富含半胱氨酸的环（A1017 T和Y1088 C）中存在复合杂合突变。据我们所知，以前没有关于A1017 T突变的报道。该患者的病理特征支持NPC具有突触核蛋白病的一个方面的概念，并且NPC的长期存活者可能发展额颞叶占优势的脑萎缩分布。
Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage disorder. Two disease-causing genes (NPC1 and NPC2) have been identified. NPC is characterized by neuronal and glial lipid storage and NFTs. Here, we report a man with juvenile-onset progressive neurological deficits, including pyramidal signs, ataxia, bulbar palsy, vertical supranuclear ophthalmoplegia, and psychiatric symptoms; death occurred at age 37 before definitive clinical diagnosis. Post mortem gross examination revealed a unique distribution of brain atrophy, predominantly in the frontal and temporal lobes. Microscopically, lipid storage in neurons and widely distributed NFTs were observed. Lipid storage cells appeared in systemic organs and filipin staining indicated intracellular cholesterol accumulation in hepatic macrophages. Electron microscopy revealed accumulation of lipids and characteristic oligolamellar inclusions. These findings suggested an NPC diagnosis. Neuronal loss and gliosis were frequently accompanied by NFTs and occurred in the frontal and temporal cortices, hippocampus, amygdala, basal forebrain, basal ganglia, thalamus, substantia nigra and brain stem nuclei. Lewy bodies (LBs) were observed in most, but not all, regions where NFTs were evident. In contrast, neuronal lipid storage occurred in more widespread areas, including the parietal and occipital cortices where neurodegeneration with either NFTs or LBs was minimal. Molecular genetic analysis demonstrated that the patient had compound heterozygous mutations in the cysteine-rich loop (A1017T and Y1088C) of the NPC1 gene. To our knowledge there has been no previous report of the A1017T mutation. The pathological features of this patient support the notion that NPC has an aspect of -synucleinopathy, and long-term survivors of NPC may develop a frontotemporal-predominant distribution of brain atrophy.