One Year of Newborn Screening for SMA - Results of a German Pilot Project
One Year of Newborn Screening for SMA - Results of a German Pilot Project
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DOI：
10.3233/jnd-190428
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Mueller-Felber, Wolfgang
中科院分区：
文献类型：
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作者：
Vill, Katharina;Koelbel, Heike;Mueller-Felber, Wolfgang
目的：脊髓性肌萎缩症（SMA）是儿童期最常见的神经退行性疾病。本研究旨在评估新生儿筛查（NBS）早期发现SMA对临床病程的影响。方法：2018年1月至2019年2月，在德国的两个联邦州巴伐利亚州和北莱茵河威斯特伐利亚州进行筛查。筛选人群中的发生率计算为每例筛选患者中检测到SMN 1基因纯合缺失的患者数量。为了了解筛选前一年新诊断SMA的发生率，进行了一项覆盖巴伐利亚州所有神经儿科中心的调查，确定了2017年和2018年的所有SMA病例。在NBS和确证性诊断试验阳性后，建议根据“美国SMA NBS多学科工作组”的建议进行治疗，建议在2和3个SMN 2拷贝的儿童中立即使用Nusinersen治疗，在≥ 4个拷贝的儿童中采用保守的严格随访策略。所有儿童每2-3个月进行一次常规标准化神经儿科检查、CHOP INTEND和HINE-2测试以及电生理检查。确定了22例SMA病例，意味着发生率为1：7524。SMN 2拷贝数分析显示，45%的患者有2个SMN 2拷贝，19%的患者有3个SMN 2拷贝，36%的患者有4个SMN 2拷贝。这些结果在截至2019年8月31日的最新统计数据中得到证实（发生率1：7089，44%有2个SMN 2拷贝，15%有3个，38%有4个）。与德国SMA发病率最新数据和巴伐利亚调查的比较证明，NBS并未导致发病率相关增加。10例有2或3个SMN 2拷贝的患者在出生后15-39天开始接受Nusinersen治疗，7/10例患者在症状发作前接受治疗。症状前治疗的患者（末次检查时的年龄：1-12个月，中位年龄8个月）在1个月至1岁时未显示肌无力。一个孩子与4 SMN 2拷贝成为症状在8 months.Conclusions的年龄：新生儿筛查，导致症状前治疗，改善儿童的遗传学证实SMA的结果。应在所有可提供治疗的国家引入新生儿SMA筛查。对于有4个SMN 2拷贝的病例，应考虑立即治疗。
Objective: Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. The study was conducted to assess the impact of early detection of SMA by newborn screening (NBS) on the clinical course of the disease.Methods: Screening was performed in two federal states of Germany, Bavaria and North Rhine Westphalia, between January 2018 and February 2019. The incidence in the screening population was calculated as number of detected patients with a homozygous deletion in the SMN1-gene per number of screened patients. To get an idea about the incidence of newly diagnosed SMA in the year prior to screening a survey covering all neuropediatric centers in the state of Bavaria was conducted, identifying all SMA-cases in 2017 and 2018. Following positive NBS and confirmatory diagnostic test, treatment was advised according to the recommendations of the "American SMA NBS Multidisciplinary Working Group" Immediate treatment with Nusinersen was recommended in children with 2 and 3 SMN2 copies and a conservative strict follow-up strategy in children with >= 4 copies. All children underwent regular standardized neuropediatric examination, CHOP INTEND and HINE-2 testing as well as electrophysiological exams every 2-3 months.Results: 165,525 children were screened. 22 cases of SMA were identified, meaning an incidence rate of 1:7524. SMN2 copy number analysis showed 2 SMN2 copies in 45% of patients, 3 SMN2 copies in 19 % and 4 SMN2 copies in 36%. These findings are confirmed in the most recent statistical data-cut from 31st August 2019 (incidence 1:7089, 2 SMN2 copies in 44%, 3 in 15% and 4 in 38%). Comparison with up-to-date German data on SMA incidence and the Bavarian survey give evidence that NBS did not lead to a relevant increase in incidence. 10 patients with 2 or 3 SMN2 copies were treated with Nusinersen, starting between 15-39 days after birth, in 7/10 patients before onset of symptoms. Presymptomatically treated patients (age at last examination: 1-12 months, median 8 months) showed no muscle weakness by the age of one month to one year. One child with 4 SMN2 copies became symptomatic at the age of 8 months.Conclusions: Newborn screening, resulting in presymptomatic treatment, improves outcome in children with genetically proven SMA. Newborn screening for SMA should be introduced in all countries where therapy is available. An immediate therapy in cases with 4 SMN2 copies should be considered.