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The Editor’s Choice for Issue 1, Volume 7
Article

Glutaric Aciduria Type I Missed by Newborn Screening: Report of Four Cases from Three Families

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Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
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Division of Metabolism, Dr. von Hauner Children’s Hospital, D-80337 Munich, Germany
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Division of Neuropediatrics, Children’s Hospital Lucerne, CH-6004 Lucerne, Switzerland
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Kinderarztpraxis Arche, CH-3270 Aarberg, Switzerland
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Austrian Newborn Screening Program, Departement of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria
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Division of Newborn Screening, Laboratory Becker & Colleagues, D-81671 Munich, Germany
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Division of Metabolism and Children’s Research Center, University Children’s Hospital Zurich, CH-8032 Zurich, Switzerland
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Swiss Newborn Screening Laboratory, University Children’s Hospital Zurich, CH-8032 Zurich, Switzerland
*
Author to whom correspondence should be addressed.
Present Address: Division of Newborn Screening, Synlab MVZ Weiden GmbH, D-92363 Weiden, Germany.
Academic Editor: Can Ficicioglu
Int. J. Neonatal Screen. 2021, 7(2), 32; https://0-doi-org.brum.beds.ac.uk/10.3390/ijns7020032
Received: 18 April 2021 / Revised: 11 June 2021 / Accepted: 13 June 2021 / Published: 18 June 2021
Glutaric aciduria type I (GA-1) is a rare autosomal-recessive disorder of the degradation of the amino acids lysine and tryptophan caused by mutations of the GCDH gene encoding glutaryl-CoA-dehydrogenase. Newborn screening (NBS) for this condition is based on elevated levels of glutarylcarnitine (C5DC) in dried blood spots (DBS). Here we report four cases from three families in whom a correctly performed NBS did not detect the condition. Glutarylcarnitine concentrations were either normal (slightly below) or slightly above the cut-off. Ratios to other acylcarnitines were also not persistently elevated. Therefore, three cases were defined as screen negative, and one case was defined as normal, after a normal control DBS sample. One patient was diagnosed after an acute encephalopathic crisis, and the other three patients had an insidious onset of the disease. GA-1 was genetically confirmed in all cases. Despite extensive efforts to increase sensitivity and specificity of NBS for GA-1, by adjusting cut-offs and introducing various ratios, the biological diversity still leads to false-negative NBS results for GA-1. View Full-Text
Keywords: glutaric aciduria type 1; newborn screening; glutaryl-carnitine; glutaric acid; 3-hydroxyglutaric acid; GCDH gene; missed cases glutaric aciduria type 1; newborn screening; glutaryl-carnitine; glutaric acid; 3-hydroxyglutaric acid; GCDH gene; missed cases
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MDPI and ACS Style

Spenger, J.; Maier, E.M.; Wechselberger, K.; Bauder, F.; Kocher, M.; Sperl, W.; Preisel, M.; Schiergens, K.A.; Konstantopoulou, V.; Röschinger, W.; Häberle, J.; Schmitt-Mechelke, T.; Wortmann, S.B.; Fingerhut, R. Glutaric Aciduria Type I Missed by Newborn Screening: Report of Four Cases from Three Families. Int. J. Neonatal Screen. 2021, 7, 32. https://0-doi-org.brum.beds.ac.uk/10.3390/ijns7020032

AMA Style

Spenger J, Maier EM, Wechselberger K, Bauder F, Kocher M, Sperl W, Preisel M, Schiergens KA, Konstantopoulou V, Röschinger W, Häberle J, Schmitt-Mechelke T, Wortmann SB, Fingerhut R. Glutaric Aciduria Type I Missed by Newborn Screening: Report of Four Cases from Three Families. International Journal of Neonatal Screening. 2021; 7(2):32. https://0-doi-org.brum.beds.ac.uk/10.3390/ijns7020032

Chicago/Turabian Style

Spenger, Johannes, Esther M. Maier, Katharina Wechselberger, Florian Bauder, Melanie Kocher, Wolfgang Sperl, Martin Preisel, Katharina A. Schiergens, Vassiliki Konstantopoulou, Wulf Röschinger, Johannes Häberle, Thomas Schmitt-Mechelke, Saskia B. Wortmann, and Ralph Fingerhut. 2021. "Glutaric Aciduria Type I Missed by Newborn Screening: Report of Four Cases from Three Families" International Journal of Neonatal Screening 7, no. 2: 32. https://0-doi-org.brum.beds.ac.uk/10.3390/ijns7020032

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