Niemann-Pick disease type C (NPC) is an autosomal recessive disorder characterized by progressive nervous degeneration. Because of the diversity of clinical symptoms and onset age, the diagnosis of this disease is difficult. Therefore, biomarker tests have attracted significant attention for earlier diagnostics. In this study, we developed a simultaneous analysis method for five urinary conjugated cholesterol metabolites, which are potential diagnostic biomarkers for a rapid, convenient, and noninvasive chemical diagnosis, using LC/MS/MS. By the method, their urinary concentrations were quantified and the NPC diagnostic performances were evaluated. The developed LC/MS/MS method showed high accuracy and satisfied all analytical method validation criteria. When the urine of healthy controls and patients with NPC was analyzed, three of five urinary conjugated cholesterol metabolite concentrations corrected by urinary creatinine were significantly higher in the patients with NPC. As a result of receiver operating characteristics analysis, these urinary metabolites might have excellent diagnostic marker performance. 3β-Sulfooxy-7β-hydroxy-5-cholenoic acid showed particularly excellent diagnostic performance with both 100% clinical sensitivity and specificity, suggesting that it is a useful NPC diagnostic marker. The urinary conjugated cholesterol metabolites exhibited high NPC diagnostic marker performance and could be used for NPC diagnosis.

中文翻译：

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五种尿胆固醇代谢产物对C型尼曼-皮克病的诊断性能调查

C型尼曼-皮克病（NPC）是常染色体隐性遗传疾病，其特征是进行性神经变性。由于临床症状和发病年龄的多样性，这种疾病的诊断很困难。因此，生物标志物测试已引起早期诊断的极大关注。在这项研究中，我们开发了一种同时分析五种尿液共轭胆固醇代谢物的方法，这是使用LC / MS / MS进行快速，便捷和无创化学诊断的潜在诊断生物标志物。通过该方法，对他们的尿液浓度进行了定量，并评估了鼻咽癌的诊断性能。所开发的LC / MS / MS方法具有很高的准确性，并满足所有分析方法的验证标准。当分析健康对照者和NPC患者的尿液时，NPC患者经尿肌酐校正的五种尿结合胆固醇代谢物浓度中有三项显着较高。作为接收器工作特性分析的结果，这些尿代谢物可能具有出色的诊断标记物性能。3β-Sulfooxy-7β-hydroxy-5-cholenoicacid显示出极佳的诊断性能，且100％的临床敏感性和特异性均表明它是有用的NPC诊断标记。尿结合胆固醇代谢物表现出较高的NPC诊断标记性能，可用于NPC诊断。这些尿代谢物可能具有出色的诊断标志物性能。3β-Sulfooxy-7β-hydroxy-5-cholenoicacid显示出极佳的诊断性能，且100％的临床敏感性和特异性均表明它是有用的NPC诊断标记。尿结合胆固醇代谢物表现出较高的NPC诊断标记性能，可用于NPC诊断。这些尿代谢物可能具有出色的诊断标志物性能。3β-Sulfooxy-7β-hydroxy-5-cholenoicacid显示出极佳的诊断性能，且100％的临床敏感性和特异性均表明它是有用的NPC诊断标记。尿结合胆固醇代谢物表现出较高的NPC诊断标记性能，可用于NPC诊断。