title: Untargeted metabolomic analysis of urine samples in the diagnosis of some inherited metabolic disorders.
abstract: BACKGROUND
  Metabolomics is becoming an important tool in clinical research and the diagnosis of human diseases. It has been used in the diagnosis of inherited metabolic disorders with pronounced biochemical abnormalities. The aim of this study was to determine if it could be applied in the diagnosis of inherited metabolic disorders (IMDs) with less clear biochemical profiles from urine samples using an untargeted metabolomic approach.
  
  
  METHODS
  A total of 14 control urine samples and 21 samples from infants with cystinuria, maple syrup urine disease, adenylosuccinate lyase deficiency and galactosemia were tested. Samples were analyzed by liquid chromatography on aminopropyl column in aqueous normal phase separation system using gradient elution of acetonitrile/ammonium acetate. Detection was performed by time-of-flight mass spectrometer fitted with electrospray ionisation in positive mode. The data were statistically processed using principal component analysis (PCA), principal component discriminant function analysis (PCA-DFA) and partial least squares (PLS) regression.
  
  
  RESULTS
  All patient samples were first distinguished from controls using unsupervised PCA. Discrimination of the patient samples was then unambiguously verified using supervised PCA-DFA. Known markers of the diseases in question were successfully confirmed and a potential new marker emerged from the PLS regression.
  
  
  CONCLUSIONS
  This study showed that untargeted metabolomics can be applied in the diagnosis of mild IMDs with less clear biochemical profiles.
authors.affiliation: Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc, Czech Republic.|Laboratory of Metabolomics, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc.
authors.forename: Hana
authors.initials: H
authors.lastname: Janeckova
authors.affiliation: Laboratory of Metabolomics, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc.|Department of Mathematical Analysis and Applications of Mathematics, Faculty of Science, Palacky University Olomouc.
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Kalivodova
authors.affiliation: Laboratory of Metabolomics, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc.
authors.forename: Lukas
authors.initials: L
authors.lastname: Najdekr
authors.affiliation: Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc, Czech Republic.|Laboratory of Metabolomics, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc.
authors.forename: David
authors.initials: D
authors.lastname: Friedecky
authors.affiliation: Department of Mathematical Analysis and Applications of Mathematics, Faculty of Science, Palacky University Olomouc.
authors.forename: Karel
authors.initials: K
authors.lastname: Hron
authors.affiliation: Department of Biotechnology, Norwegian University of Science and Technology, Sem Saelands vei 6/8, NO-7491 Trondheim, Norway.
authors.forename: Per
authors.initials: P
authors.lastname: Bruheim
authors.affiliation: Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc, Czech Republic.|Laboratory of Metabolomics, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc.
authors.forename: Tomas
authors.initials: T
authors.lastname: Adam
mesh_terms: D000264:Adenylosuccinate Lyase / Q000172:deficiency; D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000175:diagnosis; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003555:Cystinuria / Q000175:diagnosis; D005260:Female; D005693:Galactosemias / Q000175:diagnosis; D006801:Humans; D007223:Infant; D008297:Male; D008375:Maple Syrup Urine Disease / Q000175:diagnosis; D013058:Mass Spectrometry / Q000379:methods; D008659:Metabolic Diseases / Q000175:diagnosis*; D055432:Metabolomics / Q000379:methods*; D025341:Principal Component Analysis; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000264:Adenylosuccinate Lyase
keywords: inherited metabolic disorders; mass spectrometry; untargeted metabolomics