PDF(Pubmed)
Abstract：
OBJECTIVE: Mandatory newborn screening (NBS) for spinal muscular atrophy (SMA) was implemented for the first time in Italy at the end of 2021, allowing the identification and treatment of patients at an asymptomatic stage.
METHODS: DNA samples extracted from dried blood spot (DBS) from newborns in Apulia region were analysed for SMA screening by using a real-time PCR-based assay. Infants harbouring homozygous deletion of SMN1 exon 7 confirmed by diagnostic molecular tests underwent clinical and neurophysiological assessment and received a timely treatment.
RESULTS: Over the first 20 months since regional NBS introduction, four out of 42,492 (0.009%) screened children were found to carry a homozygous deletion in the exon 7 of SMN1 gene, with an annual incidence of 1:10,623. No false negatives were present. Median age at diagnosis was 7 days and median age at treatment was 20.5 days. Three of them had two copies of SMN2 and received gene therapy, while the one with three SMN2 copies was treated with nusinersen. All but one were asymptomatic at birth, showed no clinical signs of disease after a maximum follow-up of 16 months and reached motor milestones appropriate with their age. The minimum interval between diagnosis and the treatment initiation was 9 days.
CONCLUSIONS: The timely administration of disease-modifying therapies prevented presymptomatic subjects to develop disease symptoms. Mandatory NBS for SMA should be implemented on a national scale.
METHODS: DNA samples extracted from dried blood spot (DBS) from newborns in Apulia region were analysed for SMA screening by using a real-time PCR-based assay. Infants harbouring homozygous deletion of SMN1 exon 7 confirmed by diagnostic molecular tests underwent clinical and neurophysiological assessment and received a timely treatment.
RESULTS: Over the first 20 months since regional NBS introduction, four out of 42,492 (0.009%) screened children were found to carry a homozygous deletion in the exon 7 of SMN1 gene, with an annual incidence of 1:10,623. No false negatives were present. Median age at diagnosis was 7 days and median age at treatment was 20.5 days. Three of them had two copies of SMN2 and received gene therapy, while the one with three SMN2 copies was treated with nusinersen. All but one were asymptomatic at birth, showed no clinical signs of disease after a maximum follow-up of 16 months and reached motor milestones appropriate with their age. The minimum interval between diagnosis and the treatment initiation was 9 days.
CONCLUSIONS: The timely administration of disease-modifying therapies prevented presymptomatic subjects to develop disease symptoms. Mandatory NBS for SMA should be implemented on a national scale.
摘要：
目的：脊髓性肌萎缩症（SMA）的强制性新生儿筛查（NBS）于2021年底在意大利首次实施，允许在无症状阶段识别和治疗患者。
方法：使用基于实时PCR的测定法，分析了从阿普利亚地区新生儿的干血斑（DBS）中提取的DNA样本，用于SMA筛查。通过诊断分子测试证实的SMN1外显子7纯合缺失的婴儿接受了临床和神经生理学评估，并接受了及时治疗。
结果：自区域国家统计局推出以来的前20个月，在42,492名（0.009%）被筛选的儿童中有4名被发现在SMN1基因的外显子7中携带纯合缺失，年发病率为1:10,623。没有假阴性出现。诊断时的中位年龄为7天，治疗时的中位年龄为20.5天。其中三个有两个SMN2拷贝并接受了基因治疗，而具有三个SMN2拷贝的一个用nusinersen处理。除了一个人出生时没有症状，经过最长16个月的随访，未显示疾病的临床体征，并达到了与年龄相适应的运动里程碑。诊断和治疗开始之间的最小间隔为9天。
结论：及时给予疾病改善疗法可防止症状前受试者出现疾病症状。SMA的强制性国家统计局应在全国范围内实施。
方法：使用基于实时PCR的测定法，分析了从阿普利亚地区新生儿的干血斑（DBS）中提取的DNA样本，用于SMA筛查。通过诊断分子测试证实的SMN1外显子7纯合缺失的婴儿接受了临床和神经生理学评估，并接受了及时治疗。
结果：自区域国家统计局推出以来的前20个月，在42,492名（0.009%）被筛选的儿童中有4名被发现在SMN1基因的外显子7中携带纯合缺失，年发病率为1:10,623。没有假阴性出现。诊断时的中位年龄为7天，治疗时的中位年龄为20.5天。其中三个有两个SMN2拷贝并接受了基因治疗，而具有三个SMN2拷贝的一个用nusinersen处理。除了一个人出生时没有症状，经过最长16个月的随访，未显示疾病的临床体征，并达到了与年龄相适应的运动里程碑。诊断和治疗开始之间的最小间隔为9天。
结论：及时给予疾病改善疗法可防止症状前受试者出现疾病症状。SMA的强制性国家统计局应在全国范围内实施。
