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. Epub 2015 Jun 17.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Supplementary concepts

  • Coenzyme Q10 Deficiency