ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.
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.
Liang
Wen-Chen
WC
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan.
Ohkuma
Aya
A
Hayashi
Yukiko K
YK
López
Luis Carlos
LC
Hirano
Michio
M
Nonaka
Ikuya
I
Noguchi
Satoru
S
Chen
Liang-Hui
LH
Jong
Yuh-Jyh
YJ
Nishino
Ichizo
I
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
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