Abstract
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.
Highlights
Niemann-Pick disease type C (NPC) is an autosomal recessive disorder characterized by progressive nervous degeneration
The results suggested that analysis of urinary S7B- 3 -sulfooxy-7-oxo-5-cholenoic acid (5-CA) may prevent overlooking of patients with NPC with false negative results based on abnormally low concentrations due to the UGT3A1 mutation [18, 20]
A simultaneous analytical method for five urinary conjugated cholesterol metabolites identified from the urine of patients with NPC was developed using LC/MS/MS
Summary
Niemann-Pick disease type C (NPC) is an autosomal recessive disorder characterized by progressive nervous degeneration. 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. As a result of receiver operating characteristics analysis, these urinary metabolites might have excellent diagnostic marker performance. The urinary conjugated cholesterol metabolites exhibited high NPC diagnostic marker performance and could be used for NPC diagnosis.—Maekawa, M., I. Investigation of diagnostic performance of five urinary cholesterol metabolites for Niemann-Pick disease type C.
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