Direct Prediction of VLCADD Severity Using Newborn Screening Analyte Data
Schwantje, Marit Maase, Rose E Dekkers, Eugenie Ferdinandusse, Sacha Vaz, Frédéric M Hörster, Friederieke Mütze, Ulrike Grünert, Sarah C Visser, Gepke De Sain-van der Velden, Monique GM
Schwantje, Marit
Maase, Rose E
Dekkers, Eugenie
Ferdinandusse, Sacha
Vaz, Frédéric M
Hörster, Friederieke
Mütze, Ulrike
Grünert, Sarah C
Visser, Gepke
De Sain-van der Velden, Monique GM
Series / Report no.
Open Access
Type
Journal Article
Article
Article
Language
en
Date of publication
2026-03
Year of publication
Research Projects
Organizational Units
Journal Issue
Title
Direct Prediction of VLCADD Severity Using Newborn Screening Analyte Data
Translated Title
Published in
J Inherit Metab Dis 2026; 49(2):e70143
Abstract
A critical concern of newborn screening (NBS) for very-long chain acyl-CoA dehydrogenase deficiency (VLCADD) is the difficulty of predicting clinical outcomes. To address this, we investigated neonatal C18:2-carnitine concentrations as a possible predictor of VLCADD phenotype. To investigate the impact of sex, gestational age (GA) at birth, sampling day and birth weight on C18:2-carnitine, we analyzed NBS-dried blood spots (DBS) from Dutch newborns born between 2018 and 2020 (n = 209.785). After normalization for resulting confounders, C18:2-carnitine concentrations were investigated in NBS-DBS (n = 15) and neonatal plasma (n = 35) of Dutch VLCADD-patients, and in German NBS-DBS (n = 6) and correlated with clinical severity and diagnostic assays. Results showed that C18:2-carnitine concentrations were affected by GA, sampling day, birth weight and, to a lesser extent, by sex. High C18:2-carnitine, normalized for GA, sampling day and birth weight, reliably identified all VLCADD-patients with (expected) severe phenotypes. The differentiating C18:2-carnitine was identified as linoleylcarnitine. In conclusion, this study shows that neonatal C18:2-carnitine concentrations can serve to predict disease severity directly after positive NBS for VLCADD. Patients with high C18:2-carnitine concentrations can be considered "severe" and require strict dietary treatment and close monitoring. Patients with low C18:2-carnitine concentrations can be identified as "mild" and only need preventive dietary measures.