Masamitsu Maekawa1, Aya Narita2, Isamu Jinnoh3, Takashi Iida4, Thorsten Marquardt5, Eugen Mengel6, Yoshikatsu Eto7, Peter T Clayton8, Hiroaki Yamaguchi9, Nariyasu Mano9. 1. Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. Electronic address: m-maekawa@hosp.tohoku.ac.jp. 2. Division of Child Neurology, Tottori University Hospital, 86 Nishi-machi, Yonago, Tottori 683-8503, Japan. 3. Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai 980-8574, Japan. 4. College of Humanities and Sciences, Nihon University, 3-25-40 Sakurajousui, Setagaya-ku, Tokyo 156-8550, Japan. 5. Department of Pediatrics, University Hospital of Munster, Albert-Schweitzer-Campus 1 Gebaeude A13, 48149 Muenster, Germany. 6. Department of Pediatric and Adolescent Medicine, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. 7. Advanced Clinical Research Center, Institute for Neurological Disorders, Furusawa-Miyako 255, Asou-ku, Kawasaki, Kanagawa 215-0026, Japan. 8. Biochemistry Research Group, Clinical and Molecular Genetics Unit, UCL Institute of Child Health. 30 Guilford Street, London WC1N 1EH, UK. 9. Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan; Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai 980-8574, Japan.
Abstract
BACKGROUND: Niemann-Pick disease type C (NPC) is an autosomal recessive inherited disorder with progressive neuronal degeneration. Because conventional diagnostic methods are complicated and invasive, biomarker tests have drawn attention. We aimed to evaluate three urinary conjugated cholesterol metabolites as diagnostic biomarkers for NPC. METHODS: Urine samples from 23 patients with NPC, 28 healthy controls, and 7 patients with inherited metabolic disorders were analyzed. 3β-Sulfooxy-7β-N-acetylglucosaminyl-5-cholen-24-oic acid and its glycine and taurine conjugates in urine were quantified by liquid chromatography-tandem mass spectrometry. The diagnostic performance of the three metabolites and their total concentration was evaluated. RESULT: Creatinine-corrected concentrations of three metabolites and their total concentration were all significantly higher in NPC patients (0.0098 < P < .0448). The area under the receiver operating curve for all metabolites exceeded 0.95, the clinical specificity was 92-100%, and the clinical sensitivity was ~95%. In the urine of patients with other inherited metabolic diseases, the concentrations of the metabolites were lower than those in the urine of patients with NPC. CONCLUSION: These conjugated cholesterol metabolites in urine can serve as useful diagnostic markers for noninvasive screening of NPC.
BACKGROUND:Niemann-Pick disease type C (NPC) is an autosomal recessive inherited disorder with progressive neuronal degeneration. Because conventional diagnostic methods are complicated and invasive, biomarker tests have drawn attention. We aimed to evaluate three urinary conjugated cholesterol metabolites as diagnostic biomarkers for NPC. METHODS: Urine samples from 23 patients with NPC, 28 healthy controls, and 7 patients with inherited metabolic disorders were analyzed. 3β-Sulfooxy-7β-N-acetylglucosaminyl-5-cholen-24-oic acid and its glycine and taurine conjugates in urine were quantified by liquid chromatography-tandem mass spectrometry. The diagnostic performance of the three metabolites and their total concentration was evaluated. RESULT: Creatinine-corrected concentrations of three metabolites and their total concentration were all significantly higher in NPCpatients (0.0098 < P < .0448). The area under the receiver operating curve for all metabolites exceeded 0.95, the clinical specificity was 92-100%, and the clinical sensitivity was ~95%. In the urine of patients with other inherited metabolic diseases, the concentrations of the metabolites were lower than those in the urine of patients with NPC. CONCLUSION: These conjugated cholesterol metabolites in urine can serve as useful diagnostic markers for noninvasive screening of NPC.
Authors: Benita Claire Percival; Miles Gibson; Philippe B Wilson; Frances M Platt; Martin Grootveld Journal: Int J Mol Sci Date: 2020-04-05 Impact factor: 5.923