Newborn screening for primary carnitine deficiency: Who will benefit? - A retrospective cohort study

Loek Crefcoeur*, Sacha Ferdinandusse, Saskia N. van der Crabben, Eugènie Dekkers, Sabine A. Fuchs, Hidde Huidekoper, Mirian Janssen, Janneke Langendonk, Rose Maase, Monique de Sain, Estela Rubio, Francjan J. van Spronsen, Frederic Maxime Vaz, Rendelien Verschoof, Maaike de Vries, Frits Wijburg, Gepke Visser, Mirjam Langeveld

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

2 Citaten (Scopus)
27 Downloads (Pure)


Background: Newborn screening (NBS) programmes identify a wide range of disease phenotypes, which raises the question whether early identification and treatment is beneficial for all. This study aims to answer this question for primary carnitine deficiency (PCD) taking into account that NBS for PCD identifies newborns with PCD and also until then undiagnosed mothers.

Methods: We investigated clinical, genetic (variants in SLC22A5 gene) and functional (carnitine transport activity in fibroblasts) characteristics of all referred individuals through NBS (newborns and mothers) and clinically diagnosed patients with PCD (not through NBS). Disease phenotype in newborns was predicted using data from PCD mothers and cases published in literature with identical SLC22A5 variants.

Results: PCD was confirmed in 19/131 referred newborns, 37/82 referred mothers and 5 clinically diagnosed patients. Severe symptoms were observed in all clinically diagnosed patients, 1 newborn and none of the mothers identified by NBS. PCD was classified as severe in all 5 clinically diagnosed patients, 3/19 newborns and 1/37 mothers; as benign in 8/19 newborns and 36/37 mothers and as unknown in 8/19 newborns. Carnitine transport activity completely separated severe phenotype from benign phenotype (median (range): 4.0% (3.5-5.0)] vs 26% (9.5-42.5), respectively).

Conclusion: The majority of mothers and a significant proportion of newborns with PCD identified through NBS are likely to remain asymptomatic without early treatment. Conversely, a small proportion of newborns with predicted severe PCD could greatly benefit from early treatment. Genetic variants and carnitine transport activity can be used to distinguish between these groups. & amp; copy; & amp; copy; Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

Originele taal-2English
Pagina's (van-tot)1177-1185
Aantal pagina's9
TijdschriftJournal of Medical Genetics
Nummer van het tijdschrift12
StatusPublished - 1-dec.-2023


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