Pitfalls in the diagnosis of carnitine palmitoyltransferase 1 deficiency

Sarah C. Grünert; Urs Berger; Friederike Hörster; Kathrin Schwarz; Eva Thimm; Ute Spiekerkoetter; Dorothea Haas; Anke Schumann

doi:10.1515/jpem-2025-0382

Article

Pitfalls in the diagnosis of carnitine palmitoyltransferase 1 deficiency

Sarah C. Grünert , Urs Berger , Friederike Hörster , Kathrin Schwarz , Eva Thimm , Ute Spiekerkoetter , Dorothea Haas and Anke Schumann

Published/Copyright: September 29, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 12

Abstract

Objectives

Carnitine palmitoyltransferase 1 A (CPT1A) deficiency is an ultra-rare autosomal recessive disorder of the carnitine cycle caused by biallelic pathogenic variants in the CPT1A gene. It mainly presents with a hepatic phenotype and is a target disease of newborn screening programs worldwide. Disease-specific and diagnostic abnormalities of CPT1A deficiency comprise elevated concentrations of free carnitine as well as an elevated metabolite ratio [C0/(C16 + C18)] in blood, but the ideal sample material has been a matter of debate.

Methods

We present biochemical data of five CPT1A deficient patients, of whom four were diagnosed by newborn screening from dried blood spots.

Results

Our cases demonstrate that acylcarnitine profiles and especially concentrations of free carnitine can be normal in plasma in infants with CPT1AD at confirmation diagnosis after screening and during follow-up. Even the [C0/(C16 + C18)] ratio yielded normal results in some cases.

Conclusions

Our data show, that dried blood is the preferred sample material for the diagnosis of CPT1A deficiency as it is superior to serum/plasma with respect to diagnostic sensitivity and reliability in quantification of the ratio [C0/(C16 + C18)]. CPT1A deficiency can be missed, if the analysis is only performed in serum or plasma, and confirmatory diagnostics in serum or plasma after screening can be false negative.

Keywords: carnitine palmitoyltransferase 1A deficiency; CPT1A; newborn screening; dried blood spots; acylcarnitines; free carnitine

Corresponding author: Sarah C. Grünert, Faculty of Medicine, Department of Pediatrics, Children’s Hospital, Adolescent Medicine and Neonatology, Freiburg University Hospital, Breisacher Str. 62, 79106, Freiburg, Germany, E-mail: sarah.gruenert@uniklinik-freiburg.de

Acknowledgments

We are thankful to Fabian Telkämper for his technical support.

Research ethics: Ethical review and approval were not needed for that study, as the analysis only contained anonymized, retrospective analytical data from routine care.
Informed consent: Informed consent was obtained from all patients or their legal guardians.
Author contributions: Conceptualization, S.C.G. and U.B.; methodology, S.C.G. and U.B.; software, U.B.; validation, S.C.G. and U.B.; formal analysis, S.C.G. and U.B.; investigation, S.C.G. and U.B.; resources, not applicable; data curation, all authors; writing—original draft preparation, S.C.G., D.H. and U.B.; writing—review and editing, all authors; visualization, S.C.G. and U.B.; supervision, S.C.G., U.B, and A.S.; project administration, S.C.G., U.B, and A.S.; funding acquisition, not applicable. All authors have read and agreed to the published version of the manuscript.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Supporting data can be obtained from the authors upon request.

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Received: 2025-07-10

Accepted: 2025-09-15

Published Online: 2025-09-29

Published in Print: 2025-12-17

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Articles in the same Issue

https://doi.org/10.1515/jpem-2025-0382

Keywords for this article

carnitine palmitoyltransferase 1A deficiency; CPT1A; newborn screening; dried blood spots; acylcarnitines; free carnitine