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

• Published in: Journal of medical genetics Vol. 52; no. 11; pp. 779 - 783
• Main Authors: Freyer, Christoph, Stranneheim, Henrik, Naess, Karin, Mourier, Arnaud, Felser, Andrea, Maffezzini, Camilla, Lesko, Nicole, Bruhn, Helene, Engvall, Martin, Wibom, Rolf, Barbaro, Michela, Hinze, Yvonne, Magnusson, Måns, Andeer, Robin, Zetterström, Rolf H, von Döbeln, Ulrika, Wredenberg, Anna, Wedell, Anna
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.11.2015; BMJ Publishing Group
• Series: Short report
• Subjects: Age; Amino Acid Sequence; Ataxia - diagnosis; Ataxia - drug therapy; Ataxia - genetics; Biopsy; Biosynthesis; Child; Child, Preschool; Chromatography, Liquid; Creatinine; Dehydrogenases; DNA Mutational Analysis; Enzymes; Exome; Fibroblasts; Homozygote; Humans; Hydroxybenzoates - therapeutic use; Hypertension; Infant, Newborn; Male; Medicin och hälsovetenskap; 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; Musculoskeletal system; Mutation; Mutation, Missense; Ostomy; Plasma; Respiration; Sequence Alignment; Tandem Mass Spectrometry; Therapeutics; Ubiquinone - deficiency; Ubiquinone - genetics; Ultrasonic imaging; Yeast; Molecular genetics; Metabolic disorders
• DOI: 10.1136/jmedgenet-2015-102986
• ISSN: 0022-2593; 1468-6244

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