title: Coenzyme Q10 defects may be associated with a deficiency of Q10-independent mitochondrial respiratory chain complexes.
abstract: BACKGROUND
  Coenzyme Q10 (CoQ10 or ubiquinone) deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC) spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III) while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease.
  
  
  RESULTS
  To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %), thus confirming CoQ10 disease.
  
  
  CONCLUSIONS
  Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.
authors.affiliation: School of Medicine, IRCAN, UMR CNRS 7284/INSERM U1081/UNS, Nice Sophia-Antipolis University, 28 av de Valombrose, 06107, Nice Cedex 2, France. fragaki.k@chu-nice.fr.|Department of Medical Genetics, Nice Teaching Hospital, National Centre for Mitochondrial Diseases, Nice, France. fragaki.k@chu-nice.fr.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Fragaki
authors.affiliation: School of Medicine, IRCAN, UMR CNRS 7284/INSERM U1081/UNS, Nice Sophia-Antipolis University, 28 av de Valombrose, 06107, Nice Cedex 2, France. chaussenot.c@chu-nice.fr.|Department of Medical Genetics, Nice Teaching Hospital, National Centre for Mitochondrial Diseases, Nice, France. chaussenot.c@chu-nice.fr.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Chaussenot
authors.affiliation: Department of Biochemistry, Robert Debre Hospital, Paris, France. jean-francois.benoist@rdb.aphp.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Benoist
authors.affiliation: School of Medicine, IRCAN, UMR CNRS 7284/INSERM U1081/UNS, Nice Sophia-Antipolis University, 28 av de Valombrose, 06107, Nice Cedex 2, France. saadi.s@chu-nice.fr.|Department of Medical Genetics, Nice Teaching Hospital, National Centre for Mitochondrial Diseases, Nice, France. saadi.s@chu-nice.fr.
authors.forename: Samira
authors.initials: S
authors.lastname: Ait-El-Mkadem
authors.affiliation: School of Medicine, IRCAN, UMR CNRS 7284/INSERM U1081/UNS, Nice Sophia-Antipolis University, 28 av de Valombrose, 06107, Nice Cedex 2, France. bannwarth.s@chu-nice.fr.|Department of Medical Genetics, Nice Teaching Hospital, National Centre for Mitochondrial Diseases, Nice, France. bannwarth.s@chu-nice.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bannwarth
authors.affiliation: School of Medicine, IRCAN, UMR CNRS 7284/INSERM U1081/UNS, Nice Sophia-Antipolis University, 28 av de Valombrose, 06107, Nice Cedex 2, France. rouzier.c@chu-nice.fr.|Department of Medical Genetics, Nice Teaching Hospital, National Centre for Mitochondrial Diseases, Nice, France. rouzier.c@chu-nice.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Rouzier
authors.affiliation: School of Medicine, IRCAN, UMR CNRS 7284/INSERM U1081/UNS, Nice Sophia-Antipolis University, 28 av de Valombrose, 06107, Nice Cedex 2, France. cochaud.c@chu-nice.fr.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cochaud
authors.affiliation: School of Medicine, IRCAN, UMR CNRS 7284/INSERM U1081/UNS, Nice Sophia-Antipolis University, 28 av de Valombrose, 06107, Nice Cedex 2, France. paquis@hermes.unice.fr.|Department of Medical Genetics, Nice Teaching Hospital, National Centre for Mitochondrial Diseases, Nice, France. paquis@hermes.unice.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Paquis-Flucklinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001259:Ataxia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D004579:Electron Transport / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018908:Muscle Weakness / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D009132:Muscles / Q000473:pathology; D009154:Mutation; D013053:Spectrophotometry / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D014451:Ubiquinone; C024989:coenzyme Q10