Full text

Turn on search term navigation

© 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Early detection of congenital disorders by newborn screening (NBS) programs is essential to prevent or limit disease manifestation in affected neonates. These programs balance between the detection of the highest number of true cases and the lowest number of false-positives. In this case report, we describe four unrelated cases with a false-positive NBS result for very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD). Three neonates presented with decreased but not deficient VLCAD enzyme activity and two of them carried a single heterozygous ACADVL c.1844G>A mutation. Initial biochemical investigations after positive NBS referral in these infants revealed acylcarnitine and organic acid profiles resembling those seen in multiple acyl-CoA dehydrogenase deficiency (MADD). Genetic analysis did not reveal any pathogenic mutations in the genes encoding the electron transfer flavoprotein (ETF alpha and beta subunits) nor in ETF dehydrogenase. Subsequent further diagnostics revealed decreased levels of riboflavin in the newborns and oral riboflavin administration normalized the MADD-like biochemical profiles. During pregnancy, the mothers followed a vegan, vegetarian or lactose-free diet which probably caused alimentary riboflavin deficiency in the neonates. This report demonstrates that a secondary (alimentary) maternal riboflavin deficiency in combination with reduced VLCAD activity in the newborns can result in an abnormal VLCADD/MADD acylcarnitine profile and can cause false-positive NBS. We hypothesize that maternal riboflavin deficiency contributed to the false-positive VLCADD neonatal screening results.

Details

Title
Abnormal VLCADD newborn screening resembling MADD in four neonates with decreased riboflavin levels and VLCAD activity
Author
Hagemeijer, Marne C 1 ; Oussoren, Esmee 2 ; Ruijter, George J G 1 ; Onkenhout, Willem 1 ; Huidekoper, Hidde H 2 ; Ebberink, Merel S 3 ; Waterham, Hans R 3 ; Ferdinandusse, Sacha 3 ; de Vries, Maaike C 4 ; Marleen C. D. G. Huigen 4 ; Kluijtmans, Leo A J 4 ; Coene, Karlien L M 4 ; Blom, Henk J 1 

 Center for Lysosomal and Metabolic Diseases, Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands 
 Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus University Medical Center, Rotterdam, The Netherlands 
 Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands 
 Department of Laboratory Medicine, Translational Metabolic Laboratory (TML), Radboud University Medical Center, Nijmegen, The Netherlands 
Pages
12-18
Section
CASE REPORTS
Publication year
2021
Publication date
Sep 2021
Publisher
John Wiley & Sons, Inc.
ISSN
21928312
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2890095370
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.