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

  • J Med Genet. 2015 Nov;52(11):779-83. doi: 10.1136/jmedgenet-2015-102986.
Christoph Freyer  1 ,  Henrik Stranneheim  2 ,  Karin Naess  3 ,  Arnaud Mourier  4 ,  Andrea Felser  5 ,  Camilla Maffezzini  6 ,  Nicole Lesko  3 ,  Helene Bruhn  3 ,  Martin Engvall  7 ,  Rolf Wibom  3 ,  Michela Barbaro  7 ,  Yvonne Hinze  4 ,  Måns Magnusson  8 ,  Robin Andeer  8 ,  Rolf H Zetterström  7 ,  Ulrika von Döbeln  3 ,  Anna Wredenberg  1 ,  Anna Wedell  9
Affiliations
  • 1. Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • 2. Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
  • 3. Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • 4. Max Planck Institute for Biology of Ageing, Cologne, Germany.
  • 5. Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • 6. Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • 7. Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • 8. Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
  • 9. Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
PMID: 26084283 DOI: 10.1136/jmedgenet-2015-102986
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.

Keywords
Metabolic disorders; Molecular genetics.