Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid.

Abstract

BACKGROUND:

Coenzyme Q is an essential mitochondrial electron carrier, redox cofactor and a potent antioxidant in the majority of cellular membranes. Coenzyme Q deficiency has been associated with a range of metabolic diseases, as well as with some drug treatments and ageing.

METHODS:

We used whole exome sequencing (WES) to investigate patients with inherited metabolic diseases and applied a novel ultra-pressure liquid chromatography-mass spectrometry approach to measure coenzyme Q in patient samples.

RESULTS:

We identified a homozygous missense mutation in the COQ7 gene in a patient with complex mitochondrial deficiency, resulting in severely reduced coenzyme Q levels We demonstrate that the coenzyme Q analogue 2,4-dihydroxybensoic acid (2,4DHB) was able to specifically bypass the COQ7 deficiency, increase cellular coenzyme Q levels and rescue the biochemical defect in patient fibroblasts.

CONCLUSION:

We report the first patient with primary coenzyme Q deficiency due to a homozygous COQ7 mutation and a potentially beneficial treatment using 2,4DHB.

• Authors: Christoph Freyer, Henrik Stranneheim, Karin Naess, Arnaud Mourier, Andrea Felser, Camilla Maffezzini, Nicole Lesko, Helene Bruhn, Martin Engvall, Rolf Wibom, Michela Barbaro, Yvonne Hinze, Måns Magnusson, Robin Andeer, Rolf H Zetterström, Ulrika von Döbeln, Anna Wredenberg, Anna Wedell
• Journal: Journal of medical genetics (J Med Genet) Vol. 52 Issue 11 Pg. 779-83 (Nov 2015) ISSN: 1468-6244 [Electronic] England
• PMID: 26084283 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Hydroxybenzoates
• Ubiquinone
• beta-resorcylic acid
• ubiquinone 7

Topics

• Amino Acid Sequence
• Ataxia (diagnosis, drug therapy, genetics)
• Child
• Child, Preschool
• Chromatography, Liquid
• DNA Mutational Analysis
• Exome
• Homozygote
• Humans
• Hydroxybenzoates (therapeutic use)
• Infant, Newborn
• Male
• Mitochondria (genetics, metabolism)
• Mitochondrial Diseases (diagnosis, drug therapy, genetics)
• Molecular Sequence Data
• Muscle Weakness (diagnosis, drug therapy, genetics)
• Mutation, Missense
• Sequence Alignment
• Tandem Mass Spectrometry
• Ubiquinone (deficiency, genetics)