Prediction of VLCAD deficiency phenotype by a metabolic fingerprint in newborn screening bloodspots
Knottnerus, Suzan J.G.; Pras-Raves, Mia L.; van der Ham, Maria; Ferdinandusse, Sacha; Houtkooper, Riekelt H.; Schielen, Peter C.J.I.; Visser, Gepke; Wijburg, Frits A.; de Sain-van der Velden, Monique G.M.
(2020) Biochimica et Biophysica Acta - Molecular Basis of Disease, volume 1866, issue 6
(Article)
Abstract
Purpose: Newborns who test positive for very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) in newborn screening may have a severe phenotype with early onset of life-threatening symptoms but may also have an attenuated phenotype and never become symptomatic. The objective of this study is to investigate whether metabolomic profiles in dried
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bloodspots (DBS) of newborns allow early phenotypic prediction, permitting tailored treatment and follow-up. Methods: A metabolic fingerprint was generated by direct infusion high resolution mass spectrometry in DBS of VLCADD patients (n = 15) and matched controls. Multivariate analysis of the metabolomic profiles was applied to differentiate subgroups. Results: Concentration of six acylcarnitine species differed significantly between patients and controls. The concentration of C18:2- and C20:0-carnitine, 13,14-dihydroretinol and deoxycytidine monophosphate allowed separation between mild and severe patients. Two patients who could not be prognosticated on early clinical symptoms, were correctly fitted for severity in the score plot based on the untargeted metabolomics. Conclusion: Distinctive metabolomic profiles in DBS of newborns with VLCADD may allow phenotypic prognostication. The full potential of this approach as well as the underlying biochemical mechanisms need further investigation.
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Keywords: Acyl-CoA Dehydrogenase, Long-Chain/blood, Carnitine/analogs & derivatives, Child, Child, Preschool, Congenital Bone Marrow Failure Syndromes/blood, Dried Blood Spot Testing/methods, Female, Humans, Infant, Infant, Newborn, Lipid Metabolism, Inborn Errors/blood, Male, Mass Spectrometry, Metabolomics, Mitochondrial Diseases/blood, Muscular Diseases/blood, Neonatal Screening, Phenotype, Journal Article
ISSN: 0925-4439
Publisher: Elsevier
Note: Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
(Peer reviewed)