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. CONCLUSION: This study showed that untargeted metabolomics can be applied in the diagnosis of mild IMDs with less clear biochemical profiles.

• MeSH
• adenylsukcinátlyasa nedostatek   MeSH
• analýza hlavních komponent MeSH
• autistická porucha diagnóza   MeSH
• biologické markery moč   MeSH
• cystinurie diagnóza   MeSH
• dítě MeSH
• dospělí MeSH
• galaktosemie diagnóza   MeSH
• hmotnostní spektrometrie metody   MeSH
• kojenec MeSH
• lidé MeSH
• metabolické nemoci diagnóza   MeSH
• metabolomika metody   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc s močí javorového sirupu diagnóza   MeSH
• poruchy metabolismu purinů a pyrimidinů diagnóza   MeSH
• studie případů a kontrol MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Metabolomics has become an important tool in clinical research and diagnosis of human diseases. In this work we focused on the diagnosis of inherited metabolic disorders (IMDs) in plasma samples using a targeted metabolomic approach. The plasma samples were analyzed with the flow injection analysis method. All the experiments were performed on a QTRAP 5500 tandem mass spectrometer (AB SCIEX, U.S.A.) with electrospray ionization. The compounds were measured in a multiple reaction monitoring mode. We analyzed 50 control samples and 34 samples with defects in amino acid metabolism (phenylketonuria, maple syrup urine disease, tyrosinemia I, argininemia, homocystinuria, carbamoyl phosphate synthetase deficiency, ornithine transcarbamylase deficiency, nonketotic hyperglycinemia), organic acidurias (methylmalonic aciduria, propionic aciduria, glutaric aciduria I, 3-hydroxy-3-methylglutaric aciduria, isovaleric aciduria), and mitochondrial defects (medium-chain acyl-coenzyme A dehydrogenase deficiency, carnitine palmitoyltransferase II deficiency). The controls were distinguished from the patient samples by principal component analysis and hierarchical clustering. Approximately 80% of patients were clearly detected by absolute metabolite concentrations, the sum of variance for first two principle components was in the range of 44-55%. Other patient samples were assigned due to the characteristic ratio of metabolites (the sum of variance for first two principle components 77 and 83%). This study has revealed that targeted metabolomic tools with automated and unsupervised processing can be applied for the diagnosis of various IMDs.

• MeSH
• analýza hlavních komponent MeSH
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• metabolom MeSH
• metabolomika metody   MeSH
• mladiství MeSH
• předškolní dítě MeSH
• průtoková injekční analýza MeSH
• reprodukovatelnost výsledků MeSH
• shluková analýza MeSH
• tandemová hmotnostní spektrometrie MeSH
• vrozené poruchy metabolismu aminokyselin krev   diagnóza   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH