ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency

Neuromuscul Disord. 2009 Mar;19(3):212-6. doi: 10.1016/j.nmd.2009.01.008. Epub 2009 Feb 26.

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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Age of Onset
  • Asian Continental Ancestry Group / genetics
  • Carnitine / pharmacology
  • Carnitine / therapeutic use
  • Child
  • DNA Mutational Analysis
  • Electron Transport / genetics*
  • Electron-Transferring Flavoproteins / genetics*
  • Electron-Transferring Flavoproteins / metabolism
  • Energy Metabolism / drug effects
  • Energy Metabolism / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Iron-Sulfur Proteins / genetics*
  • Iron-Sulfur Proteins / metabolism
  • Male
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / drug therapy
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / genetics*
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / physiopathology*
  • Muscle Weakness / enzymology
  • Muscle Weakness / genetics
  • Muscle Weakness / physiopathology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Mutation / genetics
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Oxidoreductases Acting on CH-NH Group Donors / metabolism
  • Riboflavin / pharmacology*
  • Riboflavin / therapeutic use
  • Taiwan
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / deficiency
  • Young Adult

Substances

  • Electron-Transferring Flavoproteins
  • Iron-Sulfur Proteins
  • Ubiquinone
  • Oxidoreductases Acting on CH-NH Group Donors
  • electron-transferring-flavoprotein dehydrogenase
  • coenzyme Q10
  • Carnitine
  • Riboflavin