Department of Psychiatry, Akita University Graduate School of Medicine, Akita, Japan.
Department of Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
Orphanet J Rare Dis. 2020 Sep 29;15(1):269. doi: 10.1186/s13023-020-01531-4.
Niemann-Pick type C (NPC) is an autosomal recessive and congenital neurological disorder characterized by the accumulation of cholesterol and glycosphingolipids. Symptoms include hepatosplenomegaly, vertical supranuclear saccadic palsy, ataxia, dystonia, and dementia. Some cases frequently display narcolepsy-like symptoms, including cataplexy which was reported in 26% of all NPC patients and was more often recorded among late-infantile onset (50%) and juvenile onset (38%) patients. In this current study, we examined CSF orexin levels in the 10 patients of NPC with and without cataplexy, which supports previous findings.
Ten patients with NPC were included in the study (5 males and 5 females). NPC diagnosis was biochemically confirmed in all 10 patients, from which 8 patients with NPC1 gene were identified. We compared CSF orexin levels among NPC, narcoleptic and idiopathic hypersomnia patients.
Six NPC patients with cataplexy had low or intermediate orexin levels. In 4 cases without cataplexy, their orexin levels were normal. In 5 cases with Miglustat treatment, their symptoms stabilized or improved. For cases without Miglustat treatment, their conditions worsened generally. The CSF orexin levels of NPC patients were significantly higher than those of patients with narcolepsy-cataplexy and lower than those of patients with idiopathic hypersomnia, which was considered as the control group with normal CSF orexin levels.
Our study indicates that orexin level measurements can be an early alert of potential NPC. Low or intermediate orexin levels could further decrease due to reduction in the neuronal function in the orexin system, accelerating the patients' NPC pathophysiology. However with Miglustat treatment, the orexin levels stabilized or improved, along with other general symptoms. Although the circuitry is unclear, this supports that orexin system is indeed involved in narcolepsy-cataplexy in NPC patients.
The NPC patients with cataplexy had low or intermediate orexin levels. In the cases without cataplexy, their orexin levels were normal. Our study suggests that orexin measurements can serve as an early alert for potential NPC; furthermore, they could be a marker of therapy monitoring during a treatment.
尼曼-匹克 C 型（NPC）是一种常染色体隐性遗传性和先天性神经疾病，其特征是胆固醇和糖鞘脂的积累。症状包括肝脾肿大、垂直性核上性扫视麻痹、共济失调、肌张力障碍和痴呆。一些病例经常表现出类嗜睡症状，包括猝倒，在所有 NPC 患者中报告有 26%，在晚婴儿期发病（50%）和青少年期发病（38%）患者中更为常见。在本研究中，我们检测了 10 例 NPC 患者伴或不伴猝倒的脑脊液食欲素水平，这与先前的研究结果一致。
研究纳入了 10 例 NPC 患者（男 5 例，女 5 例）。所有 10 例患者均通过生化方法确诊 NPC，其中 8 例患者携带 NPC1 基因突变。我们比较了 NPC、发作性睡病伴猝倒和特发性嗜睡症患者的脑脊液食欲素水平。
6 例伴猝倒的 NPC 患者的食欲素水平较低或中等。4 例不伴猝倒的患者食欲素水平正常。5 例接受米格列醇治疗的患者症状稳定或改善。未接受米格列醇治疗的患者病情普遍恶化。NPC 患者的脑脊液食欲素水平明显高于发作性睡病伴猝倒患者，低于特发性嗜睡症患者，后者被认为是脑脊液食欲素水平正常的对照组。
本研究表明，食欲素水平的测量可以作为 NPC 的早期预警。由于食欲素系统神经元功能的减少，低或中等水平的食欲素可能进一步降低，加速 NPC 患者的病理生理学进展。然而，米格列醇治疗后，食欲素水平稳定或改善，同时其他一般症状也有所改善。虽然具体的神经回路尚不清楚，但这支持了食欲素系统确实参与了 NPC 患者的发作性睡病伴猝倒。
伴猝倒的 NPC 患者的食欲素水平较低或中等。不伴猝倒的患者食欲素水平正常。本研究表明，食欲素水平的测量可以作为 NPC 的早期预警，并且可能成为治疗监测的标志物。
