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Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism

Early diagnosis of inborn errors of metabolism (IEM)—a large group of congenital disorders—is critical, given that many respond well to targeted therapy. Newborn screening programs successfully capture a proportion of patients enabling early recognition and prompt initiation of therapy. For others,...

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Autores principales: Mordaunt, Dylan, Cox, David, Fuller, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072749/
https://www.ncbi.nlm.nih.gov/pubmed/32054038
http://dx.doi.org/10.3390/ijms21041195
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author Mordaunt, Dylan
Cox, David
Fuller, Maria
author_facet Mordaunt, Dylan
Cox, David
Fuller, Maria
author_sort Mordaunt, Dylan
collection PubMed
description Early diagnosis of inborn errors of metabolism (IEM)—a large group of congenital disorders—is critical, given that many respond well to targeted therapy. Newborn screening programs successfully capture a proportion of patients enabling early recognition and prompt initiation of therapy. For others, the heterogeneity in clinical presentation often confuses diagnosis with more common conditions. In the absence of family history and following clinical suspicion, the laboratory diagnosis typically begins with broad screening tests to circumscribe specialised metabolite and/or enzyme assays to identify the specific IEM. Confirmation of the biochemical diagnosis is usually achieved by identifying pathogenic genetic variants that will also enable cascade testing for family members. Unsurprisingly, this diagnostic trajectory is too often a protracted and lengthy process resulting in delays in diagnosis and, importantly, therapeutic intervention for these rare conditions is also postponed. Implementation of mass spectrometry technologies coupled with the expanding field of metabolomics is changing the landscape of diagnosing IEM as numerous metabolites, as well as enzymes, can now be measured collectively on a single mass spectrometry-based platform. As the biochemical consequences of impaired metabolism continue to be elucidated, the measurement of secondary metabolites common across groups of IEM will facilitate algorithms to further increase the efficiency of diagnosis.
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spelling pubmed-70727492020-03-19 Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism Mordaunt, Dylan Cox, David Fuller, Maria Int J Mol Sci Review Early diagnosis of inborn errors of metabolism (IEM)—a large group of congenital disorders—is critical, given that many respond well to targeted therapy. Newborn screening programs successfully capture a proportion of patients enabling early recognition and prompt initiation of therapy. For others, the heterogeneity in clinical presentation often confuses diagnosis with more common conditions. In the absence of family history and following clinical suspicion, the laboratory diagnosis typically begins with broad screening tests to circumscribe specialised metabolite and/or enzyme assays to identify the specific IEM. Confirmation of the biochemical diagnosis is usually achieved by identifying pathogenic genetic variants that will also enable cascade testing for family members. Unsurprisingly, this diagnostic trajectory is too often a protracted and lengthy process resulting in delays in diagnosis and, importantly, therapeutic intervention for these rare conditions is also postponed. Implementation of mass spectrometry technologies coupled with the expanding field of metabolomics is changing the landscape of diagnosing IEM as numerous metabolites, as well as enzymes, can now be measured collectively on a single mass spectrometry-based platform. As the biochemical consequences of impaired metabolism continue to be elucidated, the measurement of secondary metabolites common across groups of IEM will facilitate algorithms to further increase the efficiency of diagnosis. MDPI 2020-02-11 /pmc/articles/PMC7072749/ /pubmed/32054038 http://dx.doi.org/10.3390/ijms21041195 Text en © 2020 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
Mordaunt, Dylan
Cox, David
Fuller, Maria
Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism
title Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism
title_full Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism
title_fullStr Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism
title_full_unstemmed Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism
title_short Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism
title_sort metabolomics to improve the diagnostic efficiency of inborn errors of metabolism
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072749/
https://www.ncbi.nlm.nih.gov/pubmed/32054038
http://dx.doi.org/10.3390/ijms21041195
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