Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening...
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| Language: | English |
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Wiley
2013-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2013/625824 |
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| author | Serena Catarzi Anna Caciotti Janita Thusberg Rodolfo Tonin Sabrina Malvagia Giancarlo la Marca Elisabetta Pasquini Catia Cavicchi Lorenzo Ferri Maria A. Donati Federico Baronio Renzo Guerrini Sean D. Mooney Amelia Morrone |
| author_facet | Serena Catarzi Anna Caciotti Janita Thusberg Rodolfo Tonin Sabrina Malvagia Giancarlo la Marca Elisabetta Pasquini Catia Cavicchi Lorenzo Ferri Maria A. Donati Federico Baronio Renzo Guerrini Sean D. Mooney Amelia Morrone |
| author_sort | Serena Catarzi |
| collection | DOAJ |
| description | Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275*) and two new missense mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns. |
| format | Article |
| id | doaj-art-8e1cf87ea9fa47adab3cc330de821e6e |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-8e1cf87ea9fa47adab3cc330de821e6e2025-08-20T03:37:57ZengWileyThe Scientific World Journal1537-744X2013-01-01201310.1155/2013/625824625824Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular StudiesSerena Catarzi0Anna Caciotti1Janita Thusberg2Rodolfo Tonin3Sabrina Malvagia4Giancarlo la Marca5Elisabetta Pasquini6Catia Cavicchi7Lorenzo Ferri8Maria A. Donati9Federico Baronio10Renzo Guerrini11Sean D. Mooney12Amelia Morrone13Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini 24, 50139 Florence, ItalyMolecular and Cell Biology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children’s Hospital, Viale Pieraccini 24, 50139 Florence, ItalyBuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USADepartment of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini 24, 50139 Florence, ItalyNewborn Screening Biochemistry and Pharmacology Laboratory, Clinic of Paediatric Neurology, A. Meyer Children’s Hospital, Viale Pieraccini 24, 50139 Florence, ItalyDepartment of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini 24, 50139 Florence, ItalyMetabolic Disorders Unit, Neuroscience Department, A. Meyer Children’s Hospital, Viale Pieraccini 24, 50139 Florence, ItalyMolecular and Cell Biology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children’s Hospital, Viale Pieraccini 24, 50139 Florence, ItalyDepartment of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini 24, 50139 Florence, ItalyMetabolic Disorders Unit, Neuroscience Department, A. Meyer Children’s Hospital, Viale Pieraccini 24, 50139 Florence, ItalyDepartment of Pediatrics, University of Bologna, Via Massarenti 13, 40138 Bologna, ItalyDepartment of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini 24, 50139 Florence, ItalyBuck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USADepartment of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini 24, 50139 Florence, ItalyMedium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275*) and two new missense mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns.http://dx.doi.org/10.1155/2013/625824 |
| spellingShingle | Serena Catarzi Anna Caciotti Janita Thusberg Rodolfo Tonin Sabrina Malvagia Giancarlo la Marca Elisabetta Pasquini Catia Cavicchi Lorenzo Ferri Maria A. Donati Federico Baronio Renzo Guerrini Sean D. Mooney Amelia Morrone Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies The Scientific World Journal |
| title | Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies |
| title_full | Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies |
| title_fullStr | Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies |
| title_full_unstemmed | Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies |
| title_short | Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies |
| title_sort | medium chain acyl coa deficiency outlines from newborn screening in silico predictions and molecular studies |
| url | http://dx.doi.org/10.1155/2013/625824 |
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