title: ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.
abstract: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a metabolic disorder due to dysfunction of electron transfer flavoprotein (ETF) or ETF-ubiquinone oxidoreductase (ETF-QO). Mutations in ETFDH, encoding ETF-QO have been associated with both riboflavin-responsive and non-responsive MADD as well as a myopathic form of CoQ(10) deficiency, although pathomechanisms responsible for these different phenotypes are not well-defined. We performed mutation analysis in four Taiwanese MADD patients. Three novel ETFDH mutations were identified in four patients and all harbored the p.A84T mutation. Muscle CoQ(10) levels and respiratory chain activities measured in two patients were normal. Three patients improved on riboflavin together with carnitine. Our results show that not all MADD patients have CoQ(10) deficiency. Based upon our data, riboflavin and carnitine may be the first-line treatment for MADD.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Wen-Chen
authors.initials: WC
authors.lastname: Liang
authors.forename: Aya
authors.initials: A
authors.lastname: Ohkuma
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Luis Carlos
authors.initials: LC
authors.lastname: López
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
authors.forename: Liang-Hui
authors.initials: LH
authors.lastname: Chen
authors.forename: Yuh-Jyh
authors.initials: YJ
authors.lastname: Jong
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D002331:Carnitine / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D004252:DNA Mutational Analysis; D004579:Electron Transport / Q000235:genetics*; D044927:Electron-Transferring Flavoproteins / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D054069:Multiple Acyl Coenzyme A Dehydrogenase Deficiency / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D018908:Muscle Weakness / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics* / Q000378:metabolism; D012256:Riboflavin / Q000494:pharmacology* / Q000627:therapeutic use; D013624:Taiwan; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000172:deficiency; D055815:Young Adult
chemical_list: D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; D014451:Ubiquinone; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; C024989:coenzyme Q10; D002331:Carnitine; D012256:Riboflavin