Multiple acyl-coa dehydrogenase deficiency with variable presentation due to a homozygous mutation in a bedouin tribe

Orna Staretz-Chacham, Shirly Amar, Shlomo Almashanu, Ben Pode-Shakked, Ann Saada, Ohad Wormser, Eli Hershkovitz

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a fatty acid and amino acid oxidation defect caused by a deficiency of the electron-transfer flavoprotein (ETF) or the electrontransfer flavoprotein dehydrogenase (ETFDH). There are three phenotypes of the disease, two neonatal forms and one late-onset. Previous studies have suggested that there is a phenotype– genotype correlation. We report on six patients from a single Bedouin tribe, five of whom were sequenced and found to be homozygous to the same variant in the ETFDH gene, with variable severity and age of presentation. The variant, NM_004453.3 (ETFDH): c.524G>A, p.(R175H), was previously recognized as pathogenic, although it has not been reported in the literature in a homozygous state before. R175H is located near the FAD binding site, likely affecting the affinity of FAD for EFT:QO. The single homozygous ETFDH pathogenic variant was found to be causing MADD in this cohort with an unexpectedly variable severity of presentation. The difference in severity could partly be explained by early diagnosis via newborn screening and early treatment with the FAD precursor riboflavin, highlighting the importance of early detection by newborn screening.

Original languageEnglish
Article number1140
JournalGenes
Volume12
Issue number8
DOIs
StatePublished - 1 Aug 2021

Keywords

  • Electron-transfer flavoprotein (ETF)
  • Electron-transfer flavoprotein dehydrogenase (ETFDH)
  • Genotype
  • Multiple acyl-CoA dehydrogenase deficiency (MADD)
  • Phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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