A Delphi Survey Study to Formulate Statements on the Treatability of Inherited Metabolic Disorders to Decide on Eligibility for Newborn Screening

Abigail Veldman; M B Gea Kiewiet; Dineke Westra; Annet M Bosch; Marion M G Brands; René I F M de Coo; Terry G J Derks; Sabine A Fuchs; Johanna M P van den Hout; Hidde H Huidekoper; Leo A J Kluijtmans; Klaas Koop; Charlotte M A Lubout; Margaretha F Mulder; Bianca Panis; M Estela Rubio-Gozalbo; Monique G de Sain-van der Velden; Jaqueline Schaefers; Andrea B Schreuder; Gepke Visser; Ron A Wevers; Frits A Wijburg; M Rebecca Heiner-Fokkema; Francjan J van Spronsen

doi:10.3390/ijns9040056

A Delphi Survey Study to Formulate Statements on the Treatability of Inherited Metabolic Disorders to Decide on Eligibility for Newborn Screening

Int J Neonatal Screen. 2023 Oct 11;9(4):56. doi: 10.3390/ijns9040056.

Authors

Abigail Veldman¹, M B Gea Kiewiet², Dineke Westra³, Annet M Bosch⁴, Marion M G Brands⁴, René I F M de Coo⁵, Terry G J Derks¹, Sabine A Fuchs⁶, Johanna M P van den Hout⁷, Hidde H Huidekoper⁷, Leo A J Kluijtmans⁸, Klaas Koop⁶, Charlotte M A Lubout¹, Margaretha F Mulder⁴, Bianca Panis⁹, M Estela Rubio-Gozalbo¹⁰, Monique G de Sain-van der Velden¹¹, Jaqueline Schaefers⁹, Andrea B Schreuder¹, Gepke Visser^{4

6}, Ron A Wevers⁸, Frits A Wijburg⁴, M Rebecca Heiner-Fokkema¹², Francjan J van Spronsen¹

Affiliations

¹ Division of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, 9718 GZ Groningen, The Netherlands.
² Department of Genetics, University of Groningen, University Medical Center Groningen, 9718 GZ Groningen, The Netherlands.
³ Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
⁴ Department of Pediatrics, Division of Metabolic Disorders, Emma Children's Hospital, Amsterdam University Medical Centre, 1105 AZ Amsterdam, The Netherlands.
⁵ Department of Toxicogenomics, Unit Clinical Genomics, MHeNs School for Mental Health and Neuroscience, Maastricht University, 6229 ER Maastricht, The Netherlands.
⁶ Department of Metabolic Diseases, University Medical Center Utrecht, Wilhelmina Children's Hospital, 3584 EA Utrecht, The Netherlands.
⁷ Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
⁸ Department of Human Genetics, Translational Metabolic Laboratory, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
⁹ Department of Pediatrics, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
¹⁰ Department of Pediatrics and Clinical Genetics, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
¹¹ Section Metabolic Diagnostics, Department of Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
¹² Department of Laboratory Medicine, Laboratory of Metabolic Diseases, University of Groningen, University Medical Center Groningen, 9718 GZ Groningen, The Netherlands.

Abstract

The Wilson and Jungner (W&J) and Andermann criteria are meant to help select diseases eligible for population-based screening. With the introduction of next-generation sequencing (NGS) methods for newborn screening (NBS), more inherited metabolic diseases (IMDs) can technically be included, and a revision of the criteria was attempted. This study aimed to formulate statements and investigate whether those statements could elaborate on the criterion of treatability for IMDs to decide on eligibility for NBS. An online Delphi study was started among a panel of Dutch IMD experts (EPs). EPs evaluated, amended, and approved statements on treatability that were subsequently applied to 10 IMDs. After two rounds of Delphi, consensus was reached on 10 statements. Application of these statements selected 5 out of 10 IMDs proposed for this study as eligible for NBS, including 3 IMDs in the current Dutch NBS. The statement: 'The expected benefit/burden ratio of early treatment is positive and results in a significant health outcome' contributed most to decision-making. Our Delphi study resulted in 10 statements that can help to decide on eligibility for inclusion in NBS based on treatability, also showing that other criteria could be handled in a comparable way. Validation of the statements is required before these can be applied as guidance to authorities.

Keywords: Wilson and Junger criteria; inborn errors of metabolism; inherited metabolic disorders; newborn screening; next-generation sequencing; treatability; treatable.

Grants and funding

This research received no external funding. None of the authors received financial funding for this Delphi study apart from the ZonMw grant (Grant No. 50-54300-98-506) received for the NGSf4NBS project that aimed to identify and overcome technical challenges for genetic aspects of an NGS-based NBS program.