title: Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency.
abstract: BACKGROUND
  The respiratory-chain deficiencies are a broad group of largely untreatable diseases. Among them, coenzyme Q10 (ubiquinone) deficiency constitutes a subclass that deserves early and accurate diagnosis.
  
  
  METHODS
  We assessed respiratory-chain function in two siblings with severe encephalomyopathy and renal failure. We used high-performance liquid chromatography analyses, combined with radiolabelling experiments, to quantify cellular coenzyme Q10 content. Clinical follow-up and detailed biochemical investigations of respiratory chain activity were carried out over the 3 years of oral quinone administration.
  
  
  RESULTS
  Deficiency of coenzyme Q10-dependent respiratory-chain activities was identified in muscle biopsy, circulating lymphocytes, and cultured skin fibroblasts. Undetectable coenzyme Q10 and results of radiolabelling experiments in cultured fibroblasts supported the diagnosis of widespread coenzyme Q10 deficiency. Stimulation of respiration and fibroblast enzyme activities by exogenous quinones in vitro prompted us to treat the patients with oral ubidecarenone (5 mg/kg daily), which resulted in a substantial improvement of their condition over 3 years of therapy.
  
  
  CONCLUSIONS
  Particular attention should be paid to multiple quinone-responsive respiratory-chain enzyme deficiency because this rare disorder can be successfully treated by oral ubidecarenone.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital des Enfants-Malades, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: E L
authors.initials: EL
authors.lastname: Appelkvist
authors.forename: V
authors.initials: V
authors.lastname: Geromel
authors.forename: D
authors.initials: D
authors.lastname: Chretien
authors.forename: N
authors.initials: N
authors.lastname: Kadhom
authors.forename: P
authors.initials: P
authors.lastname: Edery
authors.forename: M
authors.initials: M
authors.lastname: Lebideau
authors.forename: G
authors.initials: G
authors.lastname: Dallner
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: L
authors.initials: L
authors.lastname: Ernster
authors.forename: P
authors.initials: P
authors.lastname: Rustin
mesh_terms: D000284:Administration, Oral; D000975:Antioxidants / Q000008:administration & dosage*; D001706:Biopsy; D002478:Cells, Cultured; D002648:Child; D003067:Coenzymes; D004579:Electron Transport / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology; D017237:Mitochondrial Encephalomyopathies / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D051437:Renal Insufficiency / Q000150:complications; D014451:Ubiquinone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000172:deficiency*
chemical_list: D000975:Antioxidants; D003067:Coenzymes; D014451:Ubiquinone; C024989:coenzyme Q10