Electron transfer flavoprotein deficiency: functional and molecular aspects.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a recessively inherited metabolic disorder that can be due to a deficiency of electron transfer flavoprotein (ETF) or its dehydrogenase (ETF-ubiquinone oxidoreductase). ETF is a mitochondrial matrix protein consisting of alpha- (30kDa) and beta- (28kDa) subunits encoded by the ETFA and ETFB genes, respectively. In the present study, we have analysed tissue samples from 16 unrelated patients with ETF deficiency, and we report the results of ETF activity, Western blot analysis and mutation analysis. The ETF assay provides a reliable diagnostic tool to confirm ETF deficiency in patients suspected to suffer from MADD. Activity ranged from less than 1 to 16% of controls with the most severely affected patients disclosing the lowest activity values. The majority of patients had mutations in the ETFA gene while only two of them harboured mutations in the ETFB gene. Nine novel disease-causing ETF mutations are reported.
Schiff
Manuel
M
Centre de Référence Maladies Héréditaires du Métabolisme, Service de Biochimie Pédiatrique, Hôpital Debrousse, Lyon, France. manuel.schiff@chu-lyon.fr
Froissart
Roseline
R
Olsen
Rikke K J
RK
Acquaviva
Cécile
C
Vianey-Saban
Christine
C
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency; D015153:Blotting, Western; D015331:Cohort Studies; D044927:Electron-Transferring Flavoproteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism; D010641:Phenotype
C500318:ETFA protein, human; C500319:ETFB protein, human; D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; D042964:Acyl-CoA Dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase