title: Fatal heart failure associated with CoQ10 and multiple OXPHOS deficiency in a child with propionic acidemia.
abstract: The role of a secondary respiratory chain deficiency as an additional mechanism to intoxication, leading to development of long-term energy-dependent complications, has been recently suggested in patients with propionic acidemia (PA). We show for the first time a coenzyme Q(10) (CoQ(10)) functional defect accompanied by a multiple organ oxidative phosphorylation (OXPHOS) deficiency in a child who succumbed to acute heart failure in the absence of metabolic stress. Quinone-dependent activities in the liver (complex I+III, complex II+III) were reduced, suggesting a decrease in electron transfer related to the quinone pool. The restoration of complex II+III activity after addition of exogenous ubiquinone to the assay system suggests CoQ(10) deficiency. Nevertheless, we disposed of insufficient material to perform direct measurement of CoQ(10) content in the patient's liver. Death occurred before biochemical diagnosis of OXPHOS deficiency could be made. However, this case highlights the usefulness of rapidly identifying CoQ(10) defects secondary to PA since this OXPHOS disorder has a good treatment response which could improve heart complications or prevent their appearance. Nevertheless, further studies will be necessary to determine whether CoQ(10) treatment can be useful in PA complications linked to CoQ(10) deficiency.
authors.affiliation: Department of Medical Genetics, Archet 2 Hospital, Nice Teaching Hospital, France.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Fragaki
authors.forename: Aline
authors.initials: A
authors.lastname: Cano
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Benoist
authors.forename: Odile
authors.initials: O
authors.lastname: Rigal
authors.forename: Annabelle
authors.initials: A
authors.lastname: Chaussenot
authors.forename: Cécile
authors.initials: C
authors.lastname: Rouzier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bannwarth
authors.forename: Céline
authors.initials: C
authors.lastname: Caruba
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.forename: Véronique
authors.initials: V
authors.lastname: Paquis-Flucklinger
mesh_terms: D002648:Child; D042967:Electron Transport Complex I / Q000172:deficiency; D042963:Electron Transport Complex II / Q000172:deficiency; D014450:Electron Transport Complex III / Q000172:deficiency; D006333:Heart Failure / Q000175:diagnosis*; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications* / Q000235:genetics; D056693:Propionic Acidemia / Q000150:complications* / Q000175:diagnosis*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000172:deficiency / Q000235:genetics
chemical_list: D014451:Ubiquinone; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; C024989:coenzyme Q10