Patient with multiple acyl-CoA dehydrogenase deficiency disease and ETFDH mutations benefits from riboflavin therapy: a case report

BMC Med Genomics. 2018 Apr 3;11(1):37. doi: 10.1186/s12920-018-0356-8.


Background: Lipid storage myopathy (LSM) is a diverse group of lipid metabolic disorders with great variations in the clinical phenotype and age of onset. Classical multiple acyl-CoA dehydrogenase deficiency (MADD) is known to occur secondary to mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene. Whole exome sequencing (WES) with clinical correlations can be useful in identifying genomic alterations for targeted therapy.

Case presentation: We report a patient presented with severe muscle weakness and exercise intolerance, suggestive of LSM. Diagnostic testing demonstrated lipid accumulation in muscle fibres and elevated plasma acyl carnitine levels. Exome sequencing of the proband and two of his unaffected siblings revealed compound heterozygous mutations, c.250G > A (p.Ala84Thr) and c.770A > G (p.Tyr257Cys) in the ETFDH gene as the probable causative mutations. In addition, a previously unreported variant c.1042C > T (p.Arg348Trp) in ACOT11 gene was found. This missense variant was predicted to be deleterious but its association with lipid storage in muscle is unclear. The diagnosis of MADD was established and the patient was treated with riboflavin which resulted in rapid clinical and biochemical improvement.

Conclusions: Our findings support the role of WES as an effective tool in the diagnosis of highly heterogeneous disease and this has important implications in the therapeutic strategy of LSM treatment.

Keywords: ETFDH; Lipid storage myopathy; Multiple acyl-CoA dehydrogenase deficiency; Whole exome sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Electron-Transferring Flavoproteins / genetics*
  • Female
  • Heterozygote
  • Humans
  • Iron-Sulfur Proteins / genetics*
  • Male
  • Middle Aged
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / drug therapy*
  • Multiple Acyl Coenzyme A Dehydrogenase Deficiency / genetics*
  • Mutation*
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Pedigree
  • Riboflavin / therapeutic use*


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