Niemann-Pick type C (NPC) disease is a rare lysosomal storage disorder caused by mutations in either the NPC1 or the NPC2 gene. A new class of lipids, N-acyl-O-phosphocholineserines were recently identified as NPC biomarkers. The most abundant species in this class of lipid, N-palmitoyl-O-phosphocholineserine (PPCS), was evaluated for diagnosis of NPC disease and treatment efficacy assessment with 2-hydroxypropyl-β-cyclodextrin (HPβCD) in NPC. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were developed and validated to measure PPCS in human plasma and cerebrospinal fluid (CSF). A cutoff of 248 ng/mL in plasma provided a sensitivity of 100.0% and specificity of 96.6% in identifying NPC1 patients from control and NPC1 carrier subjects. PPCS was significantly elevated in CSF from NPC1 patients, and CSF PPCS levels were significantly correlated with NPC neurological disease severity scores. Plasma and CSF PPCS did not change significantly in response to intrathetical (IT) HPβCD treatment. In an intravenous (IV) HPβCD trial, plasma PPCS in all patients was significantly reduced. These results demonstrate that plasma PPCS was able to diagnose NPC1 patients with high sensitivity and specificity, and to evaluate the peripheral treatment efficacy of IV HPβCD treatment.

中文翻译：

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N-棕榈酰-O-磷酸胆碱丝氨酸在 Niemann-Pick C 型疾病的诊断和治疗反应评估中的应用。

Niemann-Pick C 型 (NPC) 病是一种罕见的溶酶体贮积症，由 NPC1 或 NPC2 基因突变引起。一类新的脂质 N-酰基-O-磷酸胆碱丝氨酸最近被确定为 NPC 生物标志物。此类脂质中最丰富的物种 N-棕榈酰-O-磷酸胆碱 (PPCS) 被评估用于 NPC 疾病的诊断和 2-羟丙基-β-环糊精 (HPβCD) 在 NPC 中的治疗效果评估。开发并验证了液相色谱-串联质谱 (LC-MS/MS) 方法以测量人血浆和脑脊液 (CSF) 中的 PPCS。血浆中 248 ng/mL 的截止值在从对照和 NPC1 携带者受试者中识别 NPC1 患者方面提供了 100.0% 的灵敏度和 96.6% 的特异性。NPC1 患者的 CSF 中 PPCS 显着升高，和 CSF PPCS 水平与 NPC 神经系统疾病严重程度评分显着相关。血浆和 CSF PPCS 对鞘内 (IT) HPβCD 治疗没有显着变化。在一项静脉内 (IV) HPβCD 试验中，所有患者的血浆 PPCS 均显着降低。这些结果表明，血浆 PPCS 能够以高敏感性和特异性诊断 NPC1 患者，并能够评估 IV HPβCD 治疗的外周治疗效果。