Molecular analysis of 51 unrelated pedigrees with late-onset multiple acyl-CoA dehydrogenation deficiency (MADD) in southern China confirmed the most common ETFDH mutation and high carrier frequency of c.250G>A

J Mol Med (Berl). 2011 Jun;89(6):569-76. doi: 10.1007/s00109-011-0725-7. Epub 2011 Feb 24.


Multiple acyl-CoA dehydrogenation deficiency (MADD) is an autosomal recessive disease affecting amino acid, fatty acid, and choline metabolisms and is a common genetic defect responsible for lipid storage myopathy. Most forms of MADD are caused by a deficiency of electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH). However, its molecular feature has not been found uniformly in previous reports of Chinese patients. A large cohort of 56 late-onset MADD patients from 51 unrelated pedigrees in southern China was recruited to investigate a clear correlation between clinical phenotype and molecular genetic basis. All exons of ETFA, ETFB, and ETFDH, including the intron-exon boundaries, and 5' and 3' untranslated regions were directly sequenced. ETFDH deficiencies affected 94.1% (48/51) of the pedigrees. ETFDH-c.250G>A is the most common mutation, representing a high allelic frequency of 83.3% (80/96). Carrier frequency of c.250G>A is estimated to be 1.35% (7/520) in the normal population. A significant reduced expression of ETFDH was identified in the muscle of ETFDH-deficient patients. ETFDH deficiency is a major cause of riboflavin-responsive MADD in southern China, and c.250G>A is an important mutation that could be employed as a fast and reliable screening method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • China
  • Electron-Transferring Flavoproteins / genetics*
  • Electron-Transferring Flavoproteins / metabolism
  • Female
  • Gene Expression
  • Genotype
  • Heterozygote
  • 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 / metabolism
  • Muscle, Skeletal / metabolism
  • Muscular Diseases / drug therapy*
  • Muscular Diseases / genetics*
  • Mutation
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Oxidoreductases Acting on CH-NH Group Donors / metabolism
  • Phenotype
  • Riboflavin / therapeutic use*
  • Sequence Analysis, DNA


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