Wang Xin, Sun Yun, Guan Xian-Wei, Wang Yan-Yun, Hong Dong-Yang, Zhang Zhi-Lei, Li Ya-Hong, Yang Pei-Ying, Jiang Tao, Xu Zheng-Feng
Genetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Qinhuai District, 123 Tianfei Lane, Mochou Road, Nanjing, Jiangsu Province, 210004, China.
Genome Med. 2025 May 12;17(1):52. doi: 10.1186/s13073-025-01483-z.
Lysosomal storage disorders (LSDs) have a relatively high incidence among rare diseases and can lead to severe consequences if not treated promptly. However, many countries and regions have not included these disorders in their newborn screening programs, resulting in missed early detection, underdiagnosis, and delayed treatment. Newborn genomic screening (NBGS) has shown good screening effectiveness for traditional biochemical screening diseases; however, its effectiveness for LSDs has not yet been evaluated in the general newborn population.
To evaluate the outcome of NBGS for LSDs, a cohort study was conducted involving newborns recruited from Nanjing Women and Children's Healthcare Hospital in China from March 18, 2022, to September 21, 2023. All participants underwent NBGS of 15 LSDs (18 genes) via dried blood spots, followed by enzyme activity testing for NBGS-positive individuals. The study calculated the incidence and carrier rates for each LSD though NBGS, as well as the positive screening rate, the false positive rate and the positive predictive value of the screening process.
Among 22,687 newborns (11,996 males [52.88%]), 1344 (6.0%) were identified as carriers, and 30 (0.13%) were initially positive for LSDs. Of these, 4 were excluded, 15 were diagnosed as LSD-presymptomatic individuals based on enzyme deficiency and pathogenic variants conforming to inheritance patterns, and 11 remain under follow-up. The estimated combined birth incidence of LSDs in Nanjing was 1/1512, primarily including Fabry disease, Krabbe disease, glycogen storage disease type II, Niemann-Pick disease, and mucopolysaccharidosis type II. Rather than directly comparing NBGS and enzyme activity screening, this study evaluated two sequential screening strategies: (1) NBGS-first with reflex enzyme testing and (2) enzyme activity-first with reflex genomic testing. The NBGS-first strategy demonstrated higher sensitivity and specificity, with a significantly lower false positive rate and higher positive predictive values compared to the enzyme-first strategy (P < 0.05).
This study highlights the potential of NBGS to enhance early detection of presymptomatic LSD individuals, enabling timely interventions and improving newborn health outcomes. Integrating NBGS into routine newborn screening programs could provide an effective and proactive approach for LSD identification and management.
溶酶体贮积症（LSDs）在罕见病中发病率相对较高，若不及时治疗会导致严重后果。然而，许多国家和地区尚未将这些疾病纳入新生儿筛查项目，导致早期检测遗漏、诊断不足和治疗延误。新生儿基因组筛查（NBGS）对传统生化筛查疾病已显示出良好的筛查效果；然而，其对LSDs在普通新生儿群体中的有效性尚未得到评估。
为评估NBGS对LSDs的筛查结果，开展了一项队列研究，纳入了2022年3月18日至2023年9月21日在中国南京妇幼保健院招募的新生儿。所有参与者通过干血斑进行了15种LSDs（18个基因）的NBGS，随后对NBGS阳性个体进行酶活性检测。该研究通过NBGS计算了每种LSDs的发病率和携带率，以及筛查过程的阳性筛查率、假阳性率和阳性预测值。
在22687名新生儿（11996名男性[52.88%]）中，1344名（6.0%）被鉴定为携带者，30名（0.13%）最初LSDs呈阳性。其中，4名被排除，15名根据酶缺乏和符合遗传模式的致病变异被诊断为LSDs症状前个体，11名仍在随访中。南京LSDs的估计综合出生发病率为1/1512，主要包括法布里病、克拉伯病、II型糖原贮积病、尼曼-匹克病和II型黏多糖贮积症。本研究并非直接比较NBGS和酶活性筛查，而是评估了两种序贯筛查策略：（1）先进行NBGS并进行反射性酶检测，（2）先进行酶活性检测并进行反射性基因组检测。与先进行酶检测的策略相比，先进行NBGS的策略显示出更高的敏感性和特异性，假阳性率显著更低，阳性预测值更高（P<0.05）。
本研究突出了NBGS在增强LSDs症状前个体早期检测方面的潜力，能够实现及时干预并改善新生儿健康结局。将NBGS纳入常规新生儿筛查项目可为LSDs的识别和管理提供一种有效且积极主动的方法。
