Abstract
CoQ10 deficiency has been recently described in tissues of a patient with GLUT1 deficiency syndrome. Here, we investigated patients and mice with GLUT1 deficiency in order to determine whether low CoQ is a recurrent biochemical feature of this disorder, to justify CoQ10 supplementation as therapeutic option.
CoQ10 levels were investigated in plasma, white blood cells, and skin fibroblasts of 16 patients and healthy controls and in the brain, cerebellum, liver, kidney, muscle, and plasma of 4-month-old GLUT1 mutant and control mice.
CoQ10 levels in plasma did not show any difference compared with controls. Since most of the patients studied were on a ketogenic diet, which can alter CoQ10 content in plasma, we also analyzed white blood cells and cultured skin fibroblasts. Again, we found no differences. In mice, we found slightly reduced CoQ in the cerebellum, likely an epiphenomenon, and activity of the mitochondrial respiratory chain enzymes was normal.
Our data from GLUT1 deficiency patients and from GLUT1 model mice fail to support CoQ10 deficiency as a common finding in GLUT1 deficiency, suggesting that CoQ deficiency is not a direct biochemical consequence of defective glucose transport caused by molecular defects in the SLC2A1 gene.
Competing interests: None declared
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Communicated by: Shamima Rahman, FRCP, FRCPCH, PhD
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Study Funding
CMQ, KE, SD, and DCD are supported by NIH P01 HD080642-01. CMQ is supported by NICHD grant 5Â K23 HD065871 and by the Muscular Dystrophy Association (MDA). DCD receives support from the Colleen Giblin Foundation and Milestones for Children. MT and DCD receive support from the Will Foundation.
Synopsis
CoQ is not a recurrent biochemical feature of GLUT1DS; therefore, routine CoQ10 supplementation as adjuvant therapy with the ketogenic diet cannot be justified.
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Conflict of Interest
Emanuele Barca declares that he has no conflicts of interest.
Maoxue Tang declares that he has no conflicts of interest.
Kristin Engelstad declares that he has no conflicts of interest.
Giulio Kleiner declares that he has no conflicts of interest.
Salvatore DiMauro declares that he has no conflicts of interest.
Catarina M. Quinzii declares that he has no conflicts of interest.
Darryl C. De Vivo declares that he has no conflicts of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
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All institutional and national guidelines for the care and use of laboratory animals were followed.
Author Contribution
EB performed experiments and statistical analysis and wrote the manuscript, MT provided mouse samples and revised the manuscript, KE provided patients’ data and revised the manuscript, GK performed experiments and wrote the manuscript, SD conceived and designed the project and revised the manuscript, CMQ conceived and designed the project and wrote the manuscript, and DCD diagnosed and takes care of the patients, conceived and designed the project, and wrote the manuscript.
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Barca, E. et al. (2015). CoQ10 Deficiency Is Not a Common Finding in GLUT1 Deficiency Syndrome. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 29. JIMD Reports, vol 29. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_493
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DOI: https://doi.org/10.1007/8904_2015_493
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