TY - JOUR
T1 - Abnormal VLCADD newborn screening resembling MADD in four neonates with decreased riboflavin levels and VLCAD activity
AU - Hagemeijer, Marne C.
AU - Oussoren, Esmee
AU - Ruijter, George J. G.
AU - Onkenhout, Willem
AU - Huidekoper, Hidde H.
AU - Ebberink, Merel S.
AU - Waterham, Hans R.
AU - Ferdinandusse, Sacha
AU - de Vries, Maaike C.
AU - Huigen, Marleen C. D. G.
AU - Kluijtmans, Leo A. J.
AU - Coene, Karlien L. M.
AU - Blom, Henk J.
N1 - Funding Information: The authors are grateful to the legal representatives of the neonates described in this study to allow publication of this case report and Jantien Bolt-Wieringa, Monique Williams, Iris Hollink, and Marjolein Weerts for their help. Publisher Copyright: © 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - MADD
KW - VLCADD
KW - newborn screening
KW - riboflavin deficiency
UR - http://www.scopus.com/inward/record.url?scp=85114342599&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jmd2.12223
DO - https://doi.org/10.1002/jmd2.12223
M3 - Article
C2 - 34485012
SN - 2192-8304
VL - 61
SP - 12
EP - 18
JO - JIMD reports
JF - JIMD reports
IS - 1
ER -