Evaluation of 11 years of newborn screening for maple syrup urine disease in the Netherlands and a systematic review of the literature: Strategies for optimization.

评估 11 年的新生儿筛查枫糖浆尿病在荷兰和文献的系统评价 ： 优化策略。

• 发表时间: Jul 2020
• 来源期刊: JIMD Rep
• DOI: 10.1002/jmd2.12124
• PMID: 32685353
• 文章类型: Journal Article
• 作者列表: Stroek K,Boelen A,Bouva MJ,De Sain-van der Velden M,Schielen PCJI,Maase R,Engel H,Jakobs B,Kluijtmans LAJ,Mulder MF,Rubio-Gozalbo ME,van Spronsen FJ,Visser G,de Vries MC,Williams M,Heijboer AC,Kemper EA,Bosch AM

关键词: dried blood spots; leucine; maple syrup urine disease; mass‐spectrometry; newborn screening; positive predictive value; valine

Abstract

Maple syrup urine disease (MSUD) leads to severe neurological deterioration unless diagnosed early and treated immediately. We have evaluated the effectiveness of 11 years of MSUD newborn screening (NBS) in the Netherlands (screening >72 hours, referral if both total leucine (Xle) and valine ≥400 μmol/L blood) and have explored possibilities for improvement by combining our data with a systematic literature review and data from Collaborative Laboratory Integrated Reports (CLIR). Dutch MSUD NBS characteristics and accuracy were determined. The hypothetical referral numbers in the Dutch population of additional screening markers suggested by CLIR were calculated. In a systematic review, articles reporting NBS leucine concentrations of confirmed patients were included. Our data showed that NBS of 1 963 465 newborns identified 4 MSUD patients and led to 118 false-positive referrals (PPV 3.28%; incidence 1:491 000 newborns). In literature, leucine is the preferred NBS parameter. Total leucine (Xle) concentrations (mass-spectrometry) of 53 detected and 8 false-negative patients (sampling age within 25 hours in 3 patients) reported in literature ranged from 288 to 3376 (median 900) and 42 to 325 (median 209) μmol/L blood respectively. CLIR showed increasing Xle concentrations with sampling age and early NBS sampling and milder variant MSUD phenotypes with (nearly) normal biochemical profiles are causes of false-negative NBS results. We evaluated the effect of additional screening markers and established the Xle/phenylalanine ratio as a promising additional marker ratio for increasing the PPV, while maintaining high sensitivity in the Dutch MSUD NBS.

摘要

枫糖浆尿病（MSUD）导致严重的神经系统恶化，除非早期诊断并立即治疗。我们评估了荷兰11年MSUD新生儿筛查（NBS）的有效性（筛查>72小时，如果总亮氨酸（Xle）和缬氨酸≥400μmol/L血液）转诊，并通过将我们的数据与系统文献综述以及来自协作实验室综合报告（CLIR）的数据相结合，探索了改善的可能性。确定了荷兰MSUDNBS的特征和准确性。计算了CLIR建议的其他筛选标记在荷兰人群中的假设转诊人数。在系统审查中，纳入报告确诊患者NBS亮氨酸浓度的文章.我们的数据显示，1963465例新生儿的NBS鉴定出4例MSUD患者，并导致118例假阳性转诊（PPV3.28％；发生率1：491000例新生儿）。在文学中,亮氨酸是优选的NBS参数。文献报道的53例检测到的患者和8例假阴性患者（3例患者的采样年龄在25小时内）的总亮氨酸（Xle）浓度（质谱）分别为288至3376（中位数900）和42至325（中位数209）μmol/L。CLIR显示Xle浓度随采样年龄和早期NBS采样而增加，而具有（几乎）正常生化特征的轻度变异MSUD表型是假阴性NBS结果的原因。我们评估了其他筛选标记的效果，并建立了Xle/苯丙氨酸比率作为增加PPV的有希望的额外标记比率，同时保持荷兰MSUDNBS的高灵敏度。