Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe
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 electron-transfer flavoprotein dehydrogenase (ETFDH). There are three phenotypes of the disease, two neonatal forms and one late...
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MDPI AG
2021-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/8/1140 |
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| author | Orna Staretz-Chacham Shirly Amar Shlomo Almashanu Ben Pode-Shakked Ann Saada Ohad Wormser Eli Hershkovitz |
| author_facet | Orna Staretz-Chacham Shirly Amar Shlomo Almashanu Ben Pode-Shakked Ann Saada Ohad Wormser Eli Hershkovitz |
| author_sort | Orna Staretz-Chacham |
| collection | DOAJ |
| description | 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 electron-transfer 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 <i>ETFDH</i> gene, with variable severity and age of presentation. The variant, NM_004453.3 (<i>ETFDH</i>): 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 <i>ETFDH</i> 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. |
| first_indexed | 2024-03-10T08:47:37Z |
| format | Article |
| id | doaj.art-4356a2d08453454f9e39ec0de92a291e |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T08:47:37Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-4356a2d08453454f9e39ec0de92a291e2023-11-22T07:45:11ZengMDPI AGGenes2073-44252021-07-01128114010.3390/genes12081140Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin TribeOrna Staretz-Chacham0Shirly Amar1Shlomo Almashanu2Ben Pode-Shakked3Ann Saada4Ohad Wormser5Eli Hershkovitz6Metabolic Clinic, Pediatric Division, Soroka University Medical Center, Beer Sheva 84101, IsraelGenetic Lab, Soroka University Medical Center, Beer Sheva 84101, IsraelNational Newborn Screening Program, Ministry of Health, Tel-HaShomer, Ramat Gan 52621, IsraelMetabolic Disease Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 52621, IsraelHadassah Medical Center, Department of Genetics, Jerusalem 911201, IsraelThe Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84101, IsraelFaculty of Health Sciences, Ben-Gurion University, Beer Sheva 84101, IsraelMultiple 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 electron-transfer 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 <i>ETFDH</i> gene, with variable severity and age of presentation. The variant, NM_004453.3 (<i>ETFDH</i>): 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 <i>ETFDH</i> 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.https://www.mdpi.com/2073-4425/12/8/1140multiple acyl-CoA dehydrogenase deficiency (MADD)electron-transfer flavoprotein (ETF)electron-transfer flavoprotein dehydrogenase (ETFDH)genotypephenotype |
| spellingShingle | Orna Staretz-Chacham Shirly Amar Shlomo Almashanu Ben Pode-Shakked Ann Saada Ohad Wormser Eli Hershkovitz Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe Genes multiple acyl-CoA dehydrogenase deficiency (MADD) electron-transfer flavoprotein (ETF) electron-transfer flavoprotein dehydrogenase (ETFDH) genotype phenotype |
| title | Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe |
| title_full | Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe |
| title_fullStr | Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe |
| title_full_unstemmed | Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe |
| title_short | Multiple Acyl-CoA Dehydrogenase Deficiency with Variable Presentation Due to a Homozygous Mutation in a Bedouin Tribe |
| title_sort | multiple acyl coa dehydrogenase deficiency with variable presentation due to a homozygous mutation in a bedouin tribe |
| topic | multiple acyl-CoA dehydrogenase deficiency (MADD) electron-transfer flavoprotein (ETF) electron-transfer flavoprotein dehydrogenase (ETFDH) genotype phenotype |
| url | https://www.mdpi.com/2073-4425/12/8/1140 |
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