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Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics

Inborn errors of metabolism (IEMs) are a group of inherited diseases with variable incidences. IEMs are caused by disrupting enzyme activities in specific metabolic pathways by genetic mutations, either directly or indirectly by cofactor deficiencies, causing altered levels of compounds associated w...

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Detalles Bibliográficos
Autores principales: Ismail, Israa T, Showalter, Megan R, Fiehn, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835511/
https://www.ncbi.nlm.nih.gov/pubmed/31640247
http://dx.doi.org/10.3390/metabo9100242
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author Ismail, Israa T
Showalter, Megan R
Fiehn, Oliver
author_facet Ismail, Israa T
Showalter, Megan R
Fiehn, Oliver
author_sort Ismail, Israa T
collection PubMed
description Inborn errors of metabolism (IEMs) are a group of inherited diseases with variable incidences. IEMs are caused by disrupting enzyme activities in specific metabolic pathways by genetic mutations, either directly or indirectly by cofactor deficiencies, causing altered levels of compounds associated with these pathways. While IEMs may present with multiple overlapping symptoms and metabolites, early and accurate diagnosis of IEMs is critical for the long-term health of affected subjects. The prevalence of IEMs differs between countries, likely because different IEM classifications and IEM screening methods are used. Currently, newborn screening programs exclusively use targeted metabolic assays that focus on limited panels of compounds for selected IEM diseases. Such targeted approaches face the problem of false negative and false positive diagnoses that could be overcome if metabolic screening adopted analyses of a broader range of analytes. Hence, we here review the prospects of using untargeted metabolomics for IEM screening. Untargeted metabolomics and lipidomics do not rely on predefined target lists and can detect as many metabolites as possible in a sample, allowing to screen for many metabolic pathways simultaneously. Examples are given for nontargeted analyses of IEMs, and prospects and limitations of different metabolomics methods are discussed. We conclude that dedicated studies are needed to compare accuracy and robustness of targeted and untargeted methods with respect to widening the scope of IEM diagnostics.
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spelling pubmed-68355112019-11-25 Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics Ismail, Israa T Showalter, Megan R Fiehn, Oliver Metabolites Review Inborn errors of metabolism (IEMs) are a group of inherited diseases with variable incidences. IEMs are caused by disrupting enzyme activities in specific metabolic pathways by genetic mutations, either directly or indirectly by cofactor deficiencies, causing altered levels of compounds associated with these pathways. While IEMs may present with multiple overlapping symptoms and metabolites, early and accurate diagnosis of IEMs is critical for the long-term health of affected subjects. The prevalence of IEMs differs between countries, likely because different IEM classifications and IEM screening methods are used. Currently, newborn screening programs exclusively use targeted metabolic assays that focus on limited panels of compounds for selected IEM diseases. Such targeted approaches face the problem of false negative and false positive diagnoses that could be overcome if metabolic screening adopted analyses of a broader range of analytes. Hence, we here review the prospects of using untargeted metabolomics for IEM screening. Untargeted metabolomics and lipidomics do not rely on predefined target lists and can detect as many metabolites as possible in a sample, allowing to screen for many metabolic pathways simultaneously. Examples are given for nontargeted analyses of IEMs, and prospects and limitations of different metabolomics methods are discussed. We conclude that dedicated studies are needed to compare accuracy and robustness of targeted and untargeted methods with respect to widening the scope of IEM diagnostics. MDPI 2019-10-21 /pmc/articles/PMC6835511/ /pubmed/31640247 http://dx.doi.org/10.3390/metabo9100242 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ismail, Israa T
Showalter, Megan R
Fiehn, Oliver
Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics
title Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics
title_full Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics
title_fullStr Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics
title_full_unstemmed Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics
title_short Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics
title_sort inborn errors of metabolism in the era of untargeted metabolomics and lipidomics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835511/
https://www.ncbi.nlm.nih.gov/pubmed/31640247
http://dx.doi.org/10.3390/metabo9100242
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