Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability

The biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while als...

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Main Authors: Abigail Veldman, Birgit Sikkema-Raddatz, Terry G. J. Derks, Clara D. M. van Karnebeek, M. B. Gea Kiewiet, Margaretha F. Mulder, Marcel R. Nelen, M. Estela Rubio-Gozalbo, Richard J. Sinke, Monique G. de Sain-van der Velden, Gepke Visser, Maaike C. de Vries, Dineke Westra, Monique Williams, Ron A. Wevers, M. Rebecca Heiner-Fokkema, Francjan J. van Spronsen
Format: Article
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/11/1/1
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author Abigail Veldman
Birgit Sikkema-Raddatz
Terry G. J. Derks
Clara D. M. van Karnebeek
M. B. Gea Kiewiet
Margaretha F. Mulder
Marcel R. Nelen
M. Estela Rubio-Gozalbo
Richard J. Sinke
Monique G. de Sain-van der Velden
Gepke Visser
Maaike C. de Vries
Dineke Westra
Monique Williams
Ron A. Wevers
M. Rebecca Heiner-Fokkema
Francjan J. van Spronsen
author_facet Abigail Veldman
Birgit Sikkema-Raddatz
Terry G. J. Derks
Clara D. M. van Karnebeek
M. B. Gea Kiewiet
Margaretha F. Mulder
Marcel R. Nelen
M. Estela Rubio-Gozalbo
Richard J. Sinke
Monique G. de Sain-van der Velden
Gepke Visser
Maaike C. de Vries
Dineke Westra
Monique Williams
Ron A. Wevers
M. Rebecca Heiner-Fokkema
Francjan J. van Spronsen
author_sort Abigail Veldman
collection DOAJ
description The biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while also reducing secondary findings. To be eligible for inclusion in NBS, an IMD needs to fulfill the Wilson and Jungner criteria, with treatability being one of the most important criteria. In this study, we aimed to identify IMDs eligible for DNA-first NBS when considering only treatability in the context of NBS as a prerequisite. First, three independent reviewers performed a systematic literature review of the 1459 genotypic IMDs and their causative gene(s), as described in the International Classification of Inherited Metabolic Disorders (dated 1 February 2021), applying 16 criteria to exclude non-treatable disorders. Eligible disorders were then discussed in three online meetings with a project group of clinical laboratory geneticists, medical laboratory specialists specialized in IMD, and pediatricians with expertise in IMDs. Based on treatability, we identified 100 genes, causing 95 IMDs, as eligible for NBS, including 42 causal genes for the IMDs in the current biomarker-based NBS. The other 58 genes are primarily associated with treatable defects in amino acid metabolism and fatty acid oxidation. Other IMDs were excluded, most often because of insufficient literature. As the evaluation of treatability was not straightforward, we recommend the development of standardized treatability scores for the inclusion of IMDs in NBS.
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spelling doaj-art-7ea49dc19a794c59b56e564e5b0683172025-08-20T03:43:39ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2024-12-01111110.3390/ijns11010001Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on TreatabilityAbigail Veldman0Birgit Sikkema-Raddatz1Terry G. J. Derks2Clara D. M. van Karnebeek3M. B. Gea Kiewiet4Margaretha F. Mulder5Marcel R. Nelen6M. Estela Rubio-Gozalbo7Richard J. Sinke8Monique G. de Sain-van der Velden9Gepke Visser10Maaike C. de Vries11Dineke Westra12Monique Williams13Ron A. Wevers14M. Rebecca Heiner-Fokkema15Francjan J. van Spronsen16Division of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9718 GZ Groningen, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDivision of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9718 GZ Groningen, The NetherlandsDepartments of Pediatrics and Human Genetics, Emma Center for Personalized Medicine, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center, 1105 AZ Amsterdam, The NetherlandsDivision of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9718 GZ Groningen, The NetherlandsDepartments of Pediatrics and Human Genetics, Emma Center for Personalized Medicine, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center, 1105 AZ Amsterdam, The NetherlandsDepartment of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The NetherlandsDivision of Metabolic Diseases, Department of Pediatrics, Maastricht University Medical Center, 6229 HX Maastricht, The NetherlandsDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Genetics, Section Metabolic Diagnostics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartments of Pediatrics and Human Genetics, Emma Center for Personalized Medicine, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center, 1105 AZ Amsterdam, The NetherlandsDivision of Metabolic Disorders, Department of Pediatrics, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The NetherlandsCenter for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The NetherlandsLaboratory of Metabolic Diseases, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9718 GZ Groningen, The NetherlandsDivision of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9718 GZ Groningen, The NetherlandsThe biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while also reducing secondary findings. To be eligible for inclusion in NBS, an IMD needs to fulfill the Wilson and Jungner criteria, with treatability being one of the most important criteria. In this study, we aimed to identify IMDs eligible for DNA-first NBS when considering only treatability in the context of NBS as a prerequisite. First, three independent reviewers performed a systematic literature review of the 1459 genotypic IMDs and their causative gene(s), as described in the International Classification of Inherited Metabolic Disorders (dated 1 February 2021), applying 16 criteria to exclude non-treatable disorders. Eligible disorders were then discussed in three online meetings with a project group of clinical laboratory geneticists, medical laboratory specialists specialized in IMD, and pediatricians with expertise in IMDs. Based on treatability, we identified 100 genes, causing 95 IMDs, as eligible for NBS, including 42 causal genes for the IMDs in the current biomarker-based NBS. The other 58 genes are primarily associated with treatable defects in amino acid metabolism and fatty acid oxidation. Other IMDs were excluded, most often because of insufficient literature. As the evaluation of treatability was not straightforward, we recommend the development of standardized treatability scores for the inclusion of IMDs in NBS.https://www.mdpi.com/2409-515X/11/1/1inherited metabolic diseaseinborn errors of metabolismnewborn screeningtreatabilityheel prickWilson and Jungner criteria
spellingShingle Abigail Veldman
Birgit Sikkema-Raddatz
Terry G. J. Derks
Clara D. M. van Karnebeek
M. B. Gea Kiewiet
Margaretha F. Mulder
Marcel R. Nelen
M. Estela Rubio-Gozalbo
Richard J. Sinke
Monique G. de Sain-van der Velden
Gepke Visser
Maaike C. de Vries
Dineke Westra
Monique Williams
Ron A. Wevers
M. Rebecca Heiner-Fokkema
Francjan J. van Spronsen
Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability
International Journal of Neonatal Screening
inherited metabolic disease
inborn errors of metabolism
newborn screening
treatability
heel prick
Wilson and Jungner criteria
title Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability
title_full Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability
title_fullStr Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability
title_full_unstemmed Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability
title_short Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability
title_sort newborn screening by dna first systematic evaluation of the eligibility of inherited metabolic disorders based on treatability
topic inherited metabolic disease
inborn errors of metabolism
newborn screening
treatability
heel prick
Wilson and Jungner criteria
url https://www.mdpi.com/2409-515X/11/1/1
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