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Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease

Primary mitochondrial disease (PMD) is a large group of genetic disorders directly affecting mitochondrial function. Although next generation sequencing technologies have revolutionized the diagnosis of these disorders, biochemical tests remain essential and functional confirmation of the critical g...

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Autores principales: Bird, Matthew J, Adant, Isabelle, Windmolders, Petra, Vander Elst, Ingrid, Felgueira, Catarina, Altassan, Ruqaiah, Gruenert, Sarah C, Ghesquière, Bart, Witters, Peter, Cassiman, David, Vermeersch, Pieter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835216/
https://www.ncbi.nlm.nih.gov/pubmed/31658717
http://dx.doi.org/10.3390/metabo9100220
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author Bird, Matthew J
Adant, Isabelle
Windmolders, Petra
Vander Elst, Ingrid
Felgueira, Catarina
Altassan, Ruqaiah
Gruenert, Sarah C
Ghesquière, Bart
Witters, Peter
Cassiman, David
Vermeersch, Pieter
author_facet Bird, Matthew J
Adant, Isabelle
Windmolders, Petra
Vander Elst, Ingrid
Felgueira, Catarina
Altassan, Ruqaiah
Gruenert, Sarah C
Ghesquière, Bart
Witters, Peter
Cassiman, David
Vermeersch, Pieter
author_sort Bird, Matthew J
collection PubMed
description Primary mitochondrial disease (PMD) is a large group of genetic disorders directly affecting mitochondrial function. Although next generation sequencing technologies have revolutionized the diagnosis of these disorders, biochemical tests remain essential and functional confirmation of the critical genetic diagnosis. While enzymological testing of the mitochondrial oxidative phosphorylation (OXPHOS) complexes remains the gold standard, oxygraphy could offer several advantages. To this end, we compared the diagnostic performance of both techniques in a cohort of 34 genetically defined PMD patient fibroblast cell lines. We observed that oxygraphy slightly outperformed enzymology for sensitivity (79 ± 17% versus 68 ± 15%, mean and 95% CI), and had a better discriminatory power, identifying 58 ± 17% versus 35 ± 17% as “very likely” for oxygraphy and enzymology, respectively. The techniques did, however, offer synergistic diagnostic prediction, as the sensitivity rose to 88 ± 11% when considered together. Similarly, the techniques offered varying defect specific information, such as the ability of enzymology to identify isolated OXPHOS deficiencies, while oxygraphy pinpointed PDHC mutations and captured POLG mutations that were otherwise missed by enzymology. In summary, oxygraphy provides useful information for the diagnosis of PMD, and should be considered in conjunction with enzymology for the diagnosis of PMD.
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spelling pubmed-68352162019-11-25 Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease Bird, Matthew J Adant, Isabelle Windmolders, Petra Vander Elst, Ingrid Felgueira, Catarina Altassan, Ruqaiah Gruenert, Sarah C Ghesquière, Bart Witters, Peter Cassiman, David Vermeersch, Pieter Metabolites Article Primary mitochondrial disease (PMD) is a large group of genetic disorders directly affecting mitochondrial function. Although next generation sequencing technologies have revolutionized the diagnosis of these disorders, biochemical tests remain essential and functional confirmation of the critical genetic diagnosis. While enzymological testing of the mitochondrial oxidative phosphorylation (OXPHOS) complexes remains the gold standard, oxygraphy could offer several advantages. To this end, we compared the diagnostic performance of both techniques in a cohort of 34 genetically defined PMD patient fibroblast cell lines. We observed that oxygraphy slightly outperformed enzymology for sensitivity (79 ± 17% versus 68 ± 15%, mean and 95% CI), and had a better discriminatory power, identifying 58 ± 17% versus 35 ± 17% as “very likely” for oxygraphy and enzymology, respectively. The techniques did, however, offer synergistic diagnostic prediction, as the sensitivity rose to 88 ± 11% when considered together. Similarly, the techniques offered varying defect specific information, such as the ability of enzymology to identify isolated OXPHOS deficiencies, while oxygraphy pinpointed PDHC mutations and captured POLG mutations that were otherwise missed by enzymology. In summary, oxygraphy provides useful information for the diagnosis of PMD, and should be considered in conjunction with enzymology for the diagnosis of PMD. MDPI 2019-10-10 /pmc/articles/PMC6835216/ /pubmed/31658717 http://dx.doi.org/10.3390/metabo9100220 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 Article
Bird, Matthew J
Adant, Isabelle
Windmolders, Petra
Vander Elst, Ingrid
Felgueira, Catarina
Altassan, Ruqaiah
Gruenert, Sarah C
Ghesquière, Bart
Witters, Peter
Cassiman, David
Vermeersch, Pieter
Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease
title Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease
title_full Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease
title_fullStr Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease
title_full_unstemmed Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease
title_short Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease
title_sort oxygraphy versus enzymology for the biochemical diagnosis of primary mitochondrial disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835216/
https://www.ncbi.nlm.nih.gov/pubmed/31658717
http://dx.doi.org/10.3390/metabo9100220
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