Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha-L-iduronidase determinations on dried blood spots to predict symptoms.
Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha-L-iduronidase determinations on dried blood spots to predict symptoms.
复制标题
DOI：
10.1002/jmd2.12093
复制
发表时间：
2020-03-01
期刊：
影响因子：
--
通讯作者：
Tomatsu, Shunji
中科院分区：
文献类型：
--
作者：
Langan, Thomas J;Jalal, Kabir;Tomatsu, Shunji
目的：目前的新生儿粘多糖病I型筛查(NBS)存在很高的假阳性率和低的阳性预测值(PPV)。为了提高MPSI症状前预测的准确性，我们提出了一种基于已知生物标志物-α-L-艾杜糖酸酶活性(IDUA)和糖胺聚糖(GAG)硫酸肝素水平的NBS工具。方法：根据日本岐阜县5000名正常新生儿的干血点(DBS)测量数据，开发NBS工具。该工具的预测准确性在这些婴儿和7名已知患有早发性MPSI(赫勒综合征)的新生儿DBS上进行了测试。使用IDUA和HS水平的标准化自然对数的双变量分析来开发该工具。结果：该工具能够准确地预测所有早发性MPSI病例。没有正常新生儿被错误地识别为早发性MPSI，而12名正常新生儿被Gifu NBS方案错误地识别。结论：新生儿DBS中IDUA与HS的双因素分析可准确预测早期MPSI症状，控制假阳性率，加强症状前治疗。这种基于双变量分析的方法是为Krabbe病开发的，可以扩展到其他筛查的疾病。
PURPOSE: Current newborn screening (NBS) for mucopolysaccharidosis type I (MPSI) has very high false positive rates and low positive predictive values (PPVs). To improve the accuracy of presymptomatic prediction for MPSI, we propose an NBS tool based on known biomarkers, alpha-L-iduronidase enzyme activity (IDUA) and level of the glycosaminoglycan (GAG) heparan sulfate (HS).METHODS: We developed the NBS tool using measures from dried blood spots (DBS) of 5000 normal newborns from Gifu Prefecture, Japan. The tool's predictive accuracy was tested on the newborn DBS from these infants and from seven patients who were known to have early-onset MPSI (Hurler's syndrome). Bivariate analyses of the standardized natural logarithms of IDUA and HS levels were employed to develop the tool.RESULTS: Every case of early-onset MPSI was predicted correctly by the tool. No normal newborn was incorrectly identified as having early-onset MPSI, whereas 12 normal newborns were so incorrectly identified by the Gifu NBS protocol. The PPV was estimated to be 99.9%.CONCLUSIONS: Bivariate analysis of IDUA with HS in newborn DBS can accurately predict early MPSI symptoms, control false positive rates, and enhance presymptomatic treatment. This bivariate analysis-based approach, which was developed for Krabbe disease, can be extended to additional screened disorders.