Abnormal VLCADD newborn screening resembling MADD in four neonates with decreased riboflavin levels and VLCAD activity

JIMD Reports

Henk J Blom¹  Marne C. Hagemeijer¹  George J. G. Ruijter¹  Willem Onkenhout¹  Esmee Oussoren²  Hidde H. Huidekoper²  Maaike C. deVries³  Marleen C. D. G. Huigen³  Leo A. J. Kluijtmans³  Karlien L. M. Coene³  Merel S. Ebberink⁴  Sacha Ferdinandusse⁴  Hans R. Waterham⁴ 

[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;Department of Laboratory Medicine, Translational Metabolic Laboratory (TML) Radboud University Medical Center Nijmegen The Netherlands;Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam Gastroenterology Endocrinology Metabolism Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands;

关键词: MADD;    newborn screening;    riboflavin deficiency;    VLCADD;   

DOI  :  10.1002/jmd2.12223

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown