Targeted metabolomic analysis of plasma samples for the diagnosis of inherited metabolic disorders

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, USA) 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.

► We tested a targeted metabolomic approach for detection of metabolic disorders.
► The plasma samples were analyzed by flow injection analysis-tandem mass spectrometry.
► Data were evaluated by principal component analysis and hierarchical clustering.
► All 34 patients were distinguished from 50 healthy controls.