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Open AccessArticle

Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease

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Laboratory of Hepatology, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
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Metabolomics Expertise Center, Center for Cancer Biology, CCB-VIB, 3000 Leuven, Belgium
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Clinical Department of Laboratory Medicine, University Hospitals Leuven, 3000 Leuven, Belgium
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Department of Pediatrics, University Hospitals Leuven, 3000 Leuven, Belgium
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Medical Genetics Department, King Faisal Specialist Hospital and Research Center, KSA MCD, Riyadh 43228, Saudi Arabia
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Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center-University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany
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Metabolomics Expertise Center, Department of Oncology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
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Metabolic Center, University Hospitals Leuven, 3000, Leuven, Belgium
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Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work equally.
Metabolites 2019, 9(10), 220; https://doi.org/10.3390/metabo9100220
Received: 28 August 2019 / Revised: 27 September 2019 / Accepted: 9 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Genetic Metabolic Diagnostics)
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. View Full-Text
Keywords: Primary mitochondrial disease (PMD); enzymology; oxygraphy; oxidative phosphorylation (OXPHOS); respiration; diagnostics Primary mitochondrial disease (PMD); enzymology; oxygraphy; oxidative phosphorylation (OXPHOS); respiration; diagnostics
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Bird, M.J.; Adant, I.; Windmolders, P.; Vander Elst, I.; Felgueira, C.; Altassan, R.; Gruenert, S.C.; Ghesquière, B.; Witters, P.; Cassiman, D.; Vermeersch, P. Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease. Metabolites 2019, 9, 220.

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