TY - JOUR
T1 - Prediction of VLCAD deficiency phenotype by a metabolic fingerprint in newborn screening bloodspots
AU - Knottnerus, Suzan J.G.
AU - Pras-Raves, Mia L.
AU - van der Ham, Maria
AU - Ferdinandusse, Sacha
AU - Houtkooper, Riekelt H.
AU - Schielen, Peter C.J.I.
AU - Visser, Gepke
AU - Wijburg, Frits A.
AU - de Sain-van der Velden, Monique G.M.
N1 - Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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 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.
AB - 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 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.
KW - Acyl-CoA Dehydrogenase, Long-Chain/blood
KW - Carnitine/analogs & derivatives
KW - Child
KW - Child, Preschool
KW - Congenital Bone Marrow Failure Syndromes/blood
KW - Dried Blood Spot Testing/methods
KW - Female
KW - Humans
KW - Infant
KW - Infant, Newborn
KW - Lipid Metabolism, Inborn Errors/blood
KW - Male
KW - Mass Spectrometry
KW - Metabolomics
KW - Mitochondrial Diseases/blood
KW - Muscular Diseases/blood
KW - Neonatal Screening
KW - Phenotype
UR - http://www.scopus.com/inward/record.url?scp=85079758877&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2020.165725
DO - 10.1016/j.bbadis.2020.165725
M3 - Article
C2 - 32061778
AN - SCOPUS:85079758877
SN - 0925-4439
VL - 1866
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 6
M1 - 165725
ER -