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Therapeutics
Short report
Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4–dihydroxybensoic acid
  1. Christoph Freyer1,2,
  2. Henrik Stranneheim1,3,
  3. Karin Naess1,4,
  4. Arnaud Mourier5,
  5. Andrea Felser4,
  6. Camilla Maffezzini2,
  7. Nicole Lesko1,4,
  8. Helene Bruhn1,4,
  9. Martin Engvall1,6,
  10. Rolf Wibom1,4,
  11. Michela Barbaro1,6,
  12. Yvonne Hinze5,
  13. Måns Magnusson3,
  14. Robin Andeer3,
  15. Rolf H Zetterström1,6,
  16. Ulrika von Döbeln1,4,
  17. Anna Wredenberg1,2,
  18. Anna Wedell1,2,3
  1. 1Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden
  2. 2Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden
  4. 4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
  5. 5Max Planck Institute for Biology of Ageing, Cologne, Germany
  6. 6Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Dr Anna Wredenberg, Division for Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; anna.wredenberg{at}ki.se, and Prof. Anna Wedell, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; anna.wedell{at}ki.se

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.

  • Metabolic disorders
  • Molecular genetics

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/jmedgenet-2015-102986

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