Veldman Abigail, Sikkema-Raddatz Birgit, Derks Terry G J, van Karnebeek Clara D M, Kiewiet M B Gea, Mulder Margaretha F, Nelen Marcel R, Rubio-Gozalbo M Estela, Sinke Richard J, de Sain-van der Velden Monique G, Visser Gepke, de Vries Maaike C, Westra Dineke, Williams Monique, Wevers Ron A, Heiner-Fokkema M Rebecca, van Spronsen Francjan J
Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, 9718 GZ Groningen, The Netherlands.
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
Int J Neonatal Screen. 2024 Dec 28;11(1):1. doi: 10.3390/ijns11010001.
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.
基于生物标志物的荷兰新生儿筛查（NBS） panel（截至2024年）包括19种遗传性代谢疾病（IMD）。通过使用下一代测序（NGS）作为一级筛查，NBS可以扩大到包括在干血斑中缺乏可靠生化特征的IMD，同时还能减少次要发现。要符合纳入NBS的条件，一种IMD需要满足威尔逊和荣格纳标准，可治疗性是最重要的标准之一。在本研究中，我们旨在确定在仅将NBS背景下的可治疗性作为前提条件时，有资格进行DNA优先NBS的IMD。首先，三名独立评审员对1459种基因型IMD及其致病基因进行了系统的文献综述，如《遗传性代谢疾病国际分类》（2021年2月1日）所述，应用16条标准排除不可治疗的疾病。然后，在与临床实验室遗传学家、专门从事IMD的医学实验室专家以及具有IMD专业知识的儿科医生组成的项目组进行的三次在线会议中讨论了符合条件的疾病。基于可治疗性，我们确定了100个基因，导致95种IMD有资格纳入NBS，其中包括当前基于生物标志物的NBS中IMD的42个致病基因。其他58个基因主要与氨基酸代谢和脂肪酸氧化中的可治疗缺陷相关。其他IMD被排除，最常见的原因是文献不足。由于对可治疗性的评估并不直接，我们建议制定标准化的可治疗性评分，以便将IMD纳入NBS。
