Newborn screening for lysosomal storage disorders: Clinical evaluation of a two-tier strategy
Newborn screening for lysosomal storage disorders: Clinical evaluation of a two-tier strategy
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DOI：
10.1542/peds.2004-0583
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发表时间：
2004-10-01
期刊：
影响因子：
8
通讯作者：
Hopwood, JJ
中科院分区：
文献类型：
--
作者：
Meikle, PJ;Ranieri, E;Hopwood, JJ
目标。评价免疫定量测定蛋白标记物和串联质谱测定代谢物标记物在出生时鉴定溶酶体贮积症患者中的应用。对1982-1997年期间从丹麦新生儿中收集的格思里卡进行了回顾性分析。选择1982年至1997年期间在丹麦被诊断为溶酶体储存障碍（LSD； 47代表12种疾病）的患者，并从存储中检索他们的Guthrie卡片。对照卡（227）是从同一时期取回的。从南澳大利亚筛查中心（澳大利亚）收集了额外的对照卡（273张）。从2个蛋白质和94个代谢物标记中，选出15个用于lsd鉴定。鞘糖脂和寡糖标记物对法布里病、α -甘露甘露病、粘多糖病（MPS） IVA、MPS IIIA、Tay-Sachs病和i细胞病的识别灵敏度和特异性均为100%。戈谢病和唾液中毒的敏感性较低。Krabbe病、MPS II、Pompe病和Sandhoff病未发现有用的标志物。蛋白质标记物LAMP-1和皂苷C不能将LSD个体与对照人群区分开来。在目前的技术下，新生儿筛选选定的lsd是可能的。然而，需要进一步的发展，以提供一个单一的，可行的规划疾病的广泛覆盖。
Objective. To evaluate the use of protein markers using immune-quantification assays and of metabolite markers using tandem mass spectrometry for the identification, at birth, of individuals who have a lysosomal storage disorder.Methods. A retrospective analysis was conducted of Guthrie cards that were collected from newborns in Denmark during the period 1982-1997. Patients whose lysosomal storage disorder ( LSD; 47 representing 12 disorders) was diagnosed in Denmark during the period 1982 1997 were selected, and their Guthrie cards were retrieved from storage. Control cards ( 227) were retrieved from the same period. Additional control cards ( 273) were collected from the South Australian Screening Centre ( Australia).Results. From 2 protein and 94 metabolite markers, 15 were selected and evaluated for their use in the identification of LSDs. Glycosphingolipid and oligosaccharide markers showed 100% sensitivity and specificity for the identification of Fabry disease, alpha-mannosidosis, mucopolysaccharidosis (MPS) IVA, MPS IIIA, Tay-Sachs disease, and I-cell disease. Lower sensitivities were observed for Gaucher disease and sialidosis. No useful markers were identified for Krabbe disease, MPS II, Pompe disease, and Sandhoff disease. The protein markers LAMP-1 and saposin C were not able to differentiate individuals who had an LSD from the control population.Conclusions. Newborn screening for selected LSDs is possible with current technology. However, additional development is required to provide a broad coverage of disorders in a single, viable program.