Prediction of VLCAD deficiency phenotype by a metabolic fingerprint in newborn screening bloodspots

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1866

Article

Knottnerus, Suzan J. G.^1,3  Pras-Raves, Mia L.^2,3  van der Ham, Maria²  Ferdinandusse, Sacha³  Houtkooper, Riekelt H.³  Schielen, Peter C. J., I⁴  Visser, Gepke¹  Wijburg, Frits A.⁵  de Sain-van der Velden, Monique G. M.² 

[1] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Sect Metab Dis, Lundlaan 6, NL-3584 EA Utrecht, Netherlands

[2] Univ Utrecht, Univ Med Ctr Utrecht, Dept Genet, Sect Metab Diagnost, Lundlaan 6, NL-3584 EA Utrecht, Netherlands

[3] Univ Amsterdam, Lab Genet Metab Dis, Amsterdam UMC, Amsterdam Cardiovasc Sci,Amsterdam Gastroenterol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[4] Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, Reference Lab Neonatal Screening, Bilthoven, Netherlands

[5] Univ Amsterdam, Emmas Childrens Hosp, Sect Metab Dis, Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

关键词: VLCADD;    Newborn screening;    Untargeted metabolomics;   

DOI  :  10.1016/j.bbadis.2020.165725

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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