中文译文：细胞溶质尿素循环障碍个体代谢性疾病进程的严重程度调整后新生儿筛查评估。
Severity-adjusted evaluation of newborn screening on the metabolic disease course in individuals with cytosolic urea cycle disorders.
机构信息
Center for Pediatric and Adolescent Medicine, Division of Pediatric Neurology and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
Children's National Health System and The George Washington School of Medicine, Washington, DC, USA.
出版信息
Mol Genet Metab. 2020 Dec;131(4):390-397. doi: 10.1016/j.ymgme.2020.10.013. Epub 2020 Nov 7.
OBJECTIVE
The implementation of newborn screening (NBS) programs for citrullinemia type 1 (CTLN1) and argininosuccinic aciduria (ASA) is subject to controversial debate. The aim of this study was to assess the impact of NBS on the metabolic disease course and clinical outcome of affected individuals.
METHODS
In 115 individuals with CTLN1 and ASA, we compared the severity of the initial hyperammonemic episode (HAE) and the frequency of (subsequent) HAEs with the mode of diagnosis. Based on a recently established functional disease prediction model, individuals were stratified according to their predicted severe or attenuated phenotype.
RESULTS
Individuals with predicted attenuated forms of CTLN1 and ASA were overrepresented in the NBS group, while those with a predicted severe phenotype were underrepresented compared to individuals identified after the manifestation of symptoms (SX). Identification by NBS was associated with reduced severity of the initial HAE both in individuals with predicted severe and attenuated phenotypes, while it was not associated with lower frequency of (subsequent) HAEs. Similar results were obtained when including some patients diagnosed presymptomatically (i.e. prenatal testing, and high-risk family screening) in this analysis.
CONCLUSION
Since one of the major challenges of NBS outcome studies is the potential overrepresentation of individuals with predicted attenuated phenotypes in NBS cohorts, severity-adjusted evaluation of screened and unscreened individuals is important to avoid overestimation of the NBS effect. NBS enables the attenuation of the initial HAE but does not affect the frequency of subsequent metabolic decompensations in individuals with CTLN1 and ASA. Future long-term studies will need to evaluate the clinical impact of this finding, especially with regard to mortality, as well as cognitive outcome and quality of life of survivors.
目的
实施 1 型瓜氨酸血症（CTLN1）和精氨琥珀酸尿症（ASA）的新生儿筛查（NBS）方案存在争议。本研究旨在评估 NBS 对受影响个体代谢性疾病进程和临床结局的影响。
方法
在 115 例 CTLN1 和 ASA 患者中，我们比较了初始高氨血症发作（HAE）的严重程度和（后续）HAE 的频率与诊断方式的关系。基于最近建立的功能疾病预测模型，根据个体预测的严重或轻度表型对其进行分层。
结果
预测为 CTLN1 和 ASA 轻度表型的个体在 NBS 组中所占比例过高，而预测为严重表型的个体所占比例过低，与出现症状（SX）后诊断的个体相比。通过 NBS 进行识别与严重程度降低相关无论是在预测严重还是轻度表型的个体中，初始 HAE 的严重程度，而与（后续）HAE 的频率降低无关。当将此分析中一些在症状前诊断的患者（即产前检查和高危家族筛查）包括在内时，也得到了类似的结果。
结论
由于 NBS 结果研究的主要挑战之一是预测为轻度表型的个体在 NBS 队列中可能存在过度代表，因此对筛查和未筛查个体进行严重程度调整评估对于避免高估 NBS 效果很重要。NBS 可减轻初始 HAE 的严重程度，但不会影响 CTLN1 和 ASA 个体随后发生代谢失代偿的频率。未来的长期研究需要评估这一发现的临床影响，特别是死亡率，以及幸存者的认知结果和生活质量。
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