Background: The use of omics technologies in the field of neurometabolic disorders (NMD) continues to grow each year. Genomics is most widely used, but metabolomics is a powerful, complementary tool emerging in this field. With this review, we aim to assess the usefulness of untargeted metabolomics in the identification of new biomarkers in pediatric NMD for understanding the pathophysiology and for diagnostics and therapeutic strategies.
Methods: We conducted a review of the literature of untargeted metabolomics used for the study of NMD with principal manifestations in pediatric age, analyzing a total of 168 published works. Of those, only 47 fulfilled eligibility criteria and were reviewed as full text. The following variables and outcomes were assessed: type of study, disease, sample material, number of patients involved, choice of controls, methods used for untargeted metabolomics, principal metabolic findings, and pathophysiological/clinical implications.
Results: Small molecule disorders were the predominant group, accounting for 47 % of the NMD studies. Almost all the studies (93 %) were based on MS-technology, confirming its technical versatility and superior performance for metabolomic investigations. The most impactful and frequent findings were the detection of new biomarkers (55 %) and recognition of new pathophysiological mechanisms in known diseases (62 %).
Conclusions: Untargeted metabolomics is an unbiased and powerful tool in the field of NMD. Further technical improvements, larger databases and reduced analytical costs, combined with worldwide collaboration and standardization regarding preanalytical and analytical aspects, is expected to make this a cost-effective supplement to targeted analyses in the field of NMD. Are we finally entering the metabolomics era?
Keywords: Global metabolomics; Inborn errors of metabolism; Inherited metabolic disorders; Metabolomics; Neurometabolic disorders; Untargeted metabolomics.
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