Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide

In The Netherlands, newborn screening (NBS) for tyrosinemia type 1 (TT1) uses dried blood spot (DBS) succinylacetone (SUAC) as a biomarker. However, high false-positive (FP) rates and a false-negative (FN) case show that the Dutch TT1 NBS protocol is suboptimal. In search of optimization options, we...

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Main Authors: Allysa M. Kuypers, Marelle J. Bouva, J. Gerard Loeber, Anita Boelen, Eugenie Dekkers, Konstantinos Petritis, C. Austin Pickens, The ISNS Representatives, Francjan J. van Spronsen, M. Rebecca Heiner-Fokkema
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Language:English
Published: MDPI AG 2024-12-01
Series:International Journal of Neonatal Screening
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Online Access:https://www.mdpi.com/2409-515X/10/4/82
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author Allysa M. Kuypers
Marelle J. Bouva
J. Gerard Loeber
Anita Boelen
Eugenie Dekkers
Konstantinos Petritis
C. Austin Pickens
The ISNS Representatives
Francjan J. van Spronsen
M. Rebecca Heiner-Fokkema
author_facet Allysa M. Kuypers
Marelle J. Bouva
J. Gerard Loeber
Anita Boelen
Eugenie Dekkers
Konstantinos Petritis
C. Austin Pickens
The ISNS Representatives
Francjan J. van Spronsen
M. Rebecca Heiner-Fokkema
author_sort Allysa M. Kuypers
collection DOAJ
description In The Netherlands, newborn screening (NBS) for tyrosinemia type 1 (TT1) uses dried blood spot (DBS) succinylacetone (SUAC) as a biomarker. However, high false-positive (FP) rates and a false-negative (FN) case show that the Dutch TT1 NBS protocol is suboptimal. In search of optimization options, we evaluated the protocols used by other NBS programs and their performance. We distributed an online survey to NBS program representatives worldwide (<i>N</i> = 41). Questions focused on the organization and performance of the programs and on changes since implementation. Thirty-three representatives completed the survey. TT1 incidence ranged from 1/13,636 to 1/750,000. Most NBS samples are taken between 36 and 72 h after birth. Most used biomarkers were DBS SUAC (78.9%), DBS Tyrosine (Tyr; 5.3%), or DBS Tyr with second tier SUAC (15.8%). The pooled median cut-off for SUAC was 1.50 µmol/L (range 0.3–7.0 µmol/L). The median cut-off from programs using laboratory-developed tests was significantly higher (2.63 µmol/L) than the medians from programs using commercial kits (range 1.0–1.7 µmol/L). The pooled median cut-off for Tyr was 216 µmol/L (range 120–600 µmol/L). Overall positive predictive values were 27.3% for SUAC, 1.2% for Tyr solely, and 90.1% for Tyr + SUAC. One FN result was reported for TT1 NBS using SUAC, while three FN results were reported for TT1 NBS using Tyr. The NBS programs for TT1 vary worldwide in terms of analytical methods, biochemical markers, and cut-off values. There is room for improvement through method standardization, cut-off adaptation, and integration of new biomarkers. Further enhancement is likely to be achieved by the application of post-analytical tools.
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series International Journal of Neonatal Screening
spelling doaj-art-2cdcb81239fd476f8362c25d2b13c3eb2024-12-27T14:30:16ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2024-12-011048210.3390/ijns10040082Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 WorldwideAllysa M. Kuypers0Marelle J. Bouva1J. Gerard Loeber2Anita Boelen3Eugenie Dekkers4Konstantinos Petritis5C. Austin Pickens6The ISNS RepresentativesFrancjan J. van Spronsen7M. Rebecca Heiner-Fokkema8Section of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The NetherlandsCentre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The NetherlandsInternational Society for Neonatal Screening (ISNS) Office, 3721 CK Bilthoven, The NetherlandsEndocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsCentre for Population Research, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The NetherlandsNewborn Screening and Molecular Biology Branch, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USANewborn Screening and Molecular Biology Branch, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USASection of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The NetherlandsLaboratory of Metabolic Diseases, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, P.O. Box 30 001, 9700 RB Groningen, The NetherlandsIn The Netherlands, newborn screening (NBS) for tyrosinemia type 1 (TT1) uses dried blood spot (DBS) succinylacetone (SUAC) as a biomarker. However, high false-positive (FP) rates and a false-negative (FN) case show that the Dutch TT1 NBS protocol is suboptimal. In search of optimization options, we evaluated the protocols used by other NBS programs and their performance. We distributed an online survey to NBS program representatives worldwide (<i>N</i> = 41). Questions focused on the organization and performance of the programs and on changes since implementation. Thirty-three representatives completed the survey. TT1 incidence ranged from 1/13,636 to 1/750,000. Most NBS samples are taken between 36 and 72 h after birth. Most used biomarkers were DBS SUAC (78.9%), DBS Tyrosine (Tyr; 5.3%), or DBS Tyr with second tier SUAC (15.8%). The pooled median cut-off for SUAC was 1.50 µmol/L (range 0.3–7.0 µmol/L). The median cut-off from programs using laboratory-developed tests was significantly higher (2.63 µmol/L) than the medians from programs using commercial kits (range 1.0–1.7 µmol/L). The pooled median cut-off for Tyr was 216 µmol/L (range 120–600 µmol/L). Overall positive predictive values were 27.3% for SUAC, 1.2% for Tyr solely, and 90.1% for Tyr + SUAC. One FN result was reported for TT1 NBS using SUAC, while three FN results were reported for TT1 NBS using Tyr. The NBS programs for TT1 vary worldwide in terms of analytical methods, biochemical markers, and cut-off values. There is room for improvement through method standardization, cut-off adaptation, and integration of new biomarkers. Further enhancement is likely to be achieved by the application of post-analytical tools.https://www.mdpi.com/2409-515X/10/4/82tyrosinemia type 1neonatal screeningdried blood spotsinborn metabolic diseasesuccinylacetonetyrosine
spellingShingle Allysa M. Kuypers
Marelle J. Bouva
J. Gerard Loeber
Anita Boelen
Eugenie Dekkers
Konstantinos Petritis
C. Austin Pickens
The ISNS Representatives
Francjan J. van Spronsen
M. Rebecca Heiner-Fokkema
Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide
International Journal of Neonatal Screening
tyrosinemia type 1
neonatal screening
dried blood spots
inborn metabolic disease
succinylacetone
tyrosine
title Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide
title_full Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide
title_fullStr Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide
title_full_unstemmed Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide
title_short Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide
title_sort evaluation of neonatal screening programs for tyrosinemia type 1 worldwide
topic tyrosinemia type 1
neonatal screening
dried blood spots
inborn metabolic disease
succinylacetone
tyrosine
url https://www.mdpi.com/2409-515X/10/4/82
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