Late-onset form of beta-electron transfer flavoprotein deficiency

Mol Genet Metab. 2003 Apr;78(4):247-9. doi: 10.1016/s1096-7192(03)00024-6.


Multiple acyl-CoA-dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) are a group of metabolic disorders due to deficiency of either electron transfer flavoprotein (ETF) or electron transfer flavoprotein ubiquinone oxidoreductase (ETF-QO). We report the clinical features and biochemical and molecular genetic analyses of a patient with a mild late-onset form of GAII due to beta-ETF deficiency. Biochemical data showed an abnormal urine organic acid profile, low levels of free carnitine, increased levels of C(10:1n-6), and C(14:1n-9) in plasma, and decreased oxidation of [9,10-3H]palmitate and [9,10-3H]myristate in fibroblasts, suggesting MAD deficiency. In agreement with these findings, mutational analysis of the ETF/ETFDH genes demonstrated an ETFB missense mutation 124T>C in exon 2 leading to replacement of cysteine-42 with arginine (C42R), and a 604_606AAG deletion in exon 6 in the ETFB gene resulting in the deletion of lysine-202 (K202del). The present report delineates further the phenotype of mild beta-ETF deficiency and illustrates that the differential diagnosis of GAII is readily achieved by mutational analysis.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Arginine / chemistry
  • Carnitine / blood
  • Cysteine / chemistry
  • DNA Mutational Analysis
  • Electron-Transferring Flavoproteins / deficiency*
  • Electron-Transferring Flavoproteins / genetics*
  • Electrons*
  • Exons
  • Female
  • Fibroblasts / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Gene Deletion
  • Glutarates / urine
  • Humans
  • Infant, Newborn
  • Iron-Sulfur Proteins / deficiency*
  • Iron-Sulfur Proteins / genetics*
  • Lysine / chemistry
  • Mutation, Missense
  • Oxidoreductases Acting on CH-NH Group Donors / deficiency*
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Oxygen / metabolism
  • Phenotype


  • Electron-Transferring Flavoproteins
  • Glutarates
  • Iron-Sulfur Proteins
  • Arginine
  • Oxidoreductases Acting on CH-NH Group Donors
  • electron-transferring-flavoprotein dehydrogenase
  • glutaric acid
  • Lysine
  • Cysteine
  • Carnitine
  • Oxygen