Journal Article

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

Engvall, Martin, Wredenberg, Anna, Wedell, Anna, Felser, Andrea, von Döbeln, Ulrika, Stranneheim, Henrik, Andeer, Robin, Maffezzini, Camilla, Wibom, Rolf, Bruhn, Helene, Magnusson, Måns, Lesko, Nicole, Freyer, Christoph, Barbaro, Michela, Hinze, Yvonne, Naess, Karin, Mourier, Arnaud, Zetterström, Rolf H

2015

Overview

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.

• Publisher: BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: 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 / 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