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

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

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.

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