Review Article| Volume 189, P65-75, November 2017

The future perspective: metabolomics in laboratory medicine for inborn errors of metabolism

  • Yana Sandlers
    Reprint requests: Yana Sandlers, Department of Chemistry, Cleveland State University, 2323 Euclid Ave, Cleveland, OH 44115
    Department of Chemistry, Cleveland State University, Cleveland, Ohio
    Search for articles by this author
      Metabolomics can be described as a simultaneous and comprehensive analysis of small molecules in a biological sample. Recent technological and bioinformatics advances have facilitated large-scale metabolomic studies in many areas, including inborn errors of metabolism (IEMs). Despite significant improvements in the diagnosis and treatment of some IEMs, it is still challenging to understand how genetic variation affects disease progression and susceptibility. In addition, a search for new more personalized therapies and a growing demand for tools to monitor the long-term metabolic effects of existing therapies set the stage for metabolomics integration in preclinical and clinical studies. While targeted metabolomics approach is a common practice in biochemical genetics laboratories for biochemical diagnosis and monitoring of IEMs, applications of untargeted metabolomics in the clinical laboratories are still in infancy, facing some challenges. It is however, expected in the future to dramatically change the scope and utility of the clinical laboratory playing a significant role in patient management. This review provides an overview of targeted and global, large-scale metabolomic studies applied to investigate various IEMs. We discuss an existing and prospective clinical applications of metabolomics in IEMs for better diagnosis and deep understanding of complex metabolic perturbations associated with the etiology of inherited metabolic disorders.


      GC-MS (gas chromatography mass spectrometry), LC-MS (liquid chromatography mass spectrometry), CSF (Cerebrospinal fluid), IEM (inborn errors of metabolism), MALDI (matrix-assisted laser desorption ionization), SELDI (Surface-enhanced laser desorption/ionization), NMR (nuclear magnetic resonance), NBS (newborn screening), PKU (phenylketonuria), LCHAD (Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency), TFP (Trifunctional protein deficiency), MMA (methylmalonic acedimia), PA (propionic acedimia), OTC (Ornithine transcarbamylase deficiency), RDC (respiratory chain deficiencies), SLOS (Smith-Lemli Opitz syndrome), CTX (Cerebrotendinous xanthomatosis), RP (Reverse phase), HILIC (hydrophilic interaction liquid chromatography), ROC (receiver-operating characteristic), AUC (Area under the curve)
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