Medium-chain acyl-CoA deficiency: Outlines from newborn screening, in silico predictions, and molecular studies

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number625824
JournalTheScientificWorldJournal
Volume2013
DOIs
Publication statusPublished - 2013

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Acyl-CoA Dehydrogenase
Acyl Coenzyme A
Computer Simulation
mutation
Screening
molecular analysis
Newborn Infant
allele
prediction
fasting
bioinformatics
Alleles
Lethargy
Mutation
brain
liquid chromatography
Liquid chromatography
Missense Mutation
fatty acid
Bioinformatics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Medicine(all)

Cite this

Catarzi, S., Caciotti, A., Thusberg, J., Tonin, R., Malvagia, S., La Marca, G., ... Morrone, A. (2013). Medium-chain acyl-CoA deficiency: Outlines from newborn screening, in silico predictions, and molecular studies. TheScientificWorldJournal, 2013, [625824]. https://doi.org/10.1155/2013/625824

Medium-chain acyl-CoA deficiency : Outlines from newborn screening, in silico predictions, and molecular studies. / Catarzi, Serena; Caciotti, Anna; Thusberg, Janita; Tonin, Rodolfo; Malvagia, Sabrina; La Marca, Giancarlo; Pasquini, Elisabetta; Cavicchi, Catia; Ferri, Lorenzo; Donati, Maria A.; Baronio, Federico; Guerrini, Renzo; Mooney, Sean D.; Morrone, Amelia.

In: TheScientificWorldJournal, Vol. 2013, 625824, 2013.

Research output: Contribution to journalArticle

Catarzi, S, Caciotti, A, Thusberg, J, Tonin, R, Malvagia, S, La Marca, G, Pasquini, E, Cavicchi, C, Ferri, L, Donati, MA, Baronio, F, Guerrini, R, Mooney, SD & Morrone, A 2013, 'Medium-chain acyl-CoA deficiency: Outlines from newborn screening, in silico predictions, and molecular studies', TheScientificWorldJournal, vol. 2013, 625824. https://doi.org/10.1155/2013/625824
Catarzi, Serena ; Caciotti, Anna ; Thusberg, Janita ; Tonin, Rodolfo ; Malvagia, Sabrina ; La Marca, Giancarlo ; Pasquini, Elisabetta ; Cavicchi, Catia ; Ferri, Lorenzo ; Donati, Maria A. ; Baronio, Federico ; Guerrini, Renzo ; Mooney, Sean D. ; Morrone, Amelia. / Medium-chain acyl-CoA deficiency : Outlines from newborn screening, in silico predictions, and molecular studies. In: TheScientificWorldJournal. 2013 ; Vol. 2013.
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