Newborn screening for lysosomal storage disorders
Newborn screening for lysosomal storage disorders
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DOI：
10.1016/j.ymgme.2006.02.013
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发表时间：
2006-08-01
影响因子：
3.8
通讯作者：
Hopwood, John J.
中科院分区：
文献类型：
--
作者：
Meikle, Peter J.;Grasby, Dallas J.;Hopwood, John J.
溶酶体贮积症（LSD）是一种慢性进行性疾病，对患者和家庭造成了毁灭性的影响。大多数患者在出生时临床正常，但在儿童早期出现症状。尽管没有治愈性治疗，但有一些治疗选择可以改善生活质量。为了实现这一目标，迫切需要对新生儿进行筛查，以便在出现严重不可逆病理之前及早发现受影响的个体。我们开发了一种多种免疫定量检测I - I不同溶酶体蛋白的方法，用于LSD患者的鉴定，并在一项回顾性研究中使用来自；随后诊断为LSD的新生儿（n = 19, 6种不同的LSD），诊断为LSD的个体（n = 92, 11种不同的LSD），新生儿对照组（n = 433）和成人对照组（n = 200）。所有粘多糖病I型（MPS I）、MPS II型、MPS IIIA型、MPS VI型、异色性脑白质营养不良、Niemann-Pick病A/GB型和多种硫酸酯酶缺乏症患者均可通过酶水平较对照组降低来识别。所有II/III型粘脂病患者均通过几种溶酶体酶的升高来确定，高于对照范围。大多数法布里病、庞贝病和戈谢病患者是通过单一蛋白差异或多种蛋白标记谱来鉴定的。新生儿多重LSD筛查可以通过对一组溶酶体蛋白进行多重免疫定量来实现。通过进一步验证，该方法可以很容易地纳入现有的筛查实验室，并将对患者管理和家庭咨询产生重大影响。(c) 2006爱思唯尔公司版权所有。
Lysosomal storage disorders (LSD) are chronic progressive diseases that have a devastating impact on the patient and family. Most patients are clinically normal at birth but develop symptoms early in childhood. Despite no curative treatment, a number of therapeutic options are available to improve quality of life. To achieve this, there is a pressing need for newborn screening to identify affected individuals early, before the onset of severe irreversible pathology. We have developed a multiplexed immune-quantification assay of I I different lysosomal proteins for the identification of individuals with an LSD and evaluated this assay in a retrospective study using blood-spots from; newborns subsequently diagnosed with an LSD (n = 19, six different LSD), individuals sampled after diagnosis of an LSD (n = 92, 11 different LSD), newborn controls (n = 433), and adult controls (n = 200). All patients with mucopolysaccharidosis type I (MPS I), MPS II, MPS IIIA, MPS VI, metachromatic leukodystrophy, Niemann-Pick disease type A/GB, and multiple sulfatase deficiency could be identified by reduced enzyme levels compared to controls. All mucolipidosis type II/III patients were identified by the elevation of several lysosomal enzymes, above the control range. Most Fabry, Pompe, and Gaucher disease patients were identified from either single protein differences or profiles of multiple protein markers. Newborn screening for multiple LSD:is achievable using multiplexed immune-quantification of a panel of lysosomal proteins. With further validation, this method could be readily incorporated into existing screening laboratories and will have a substantial impact on patient management and counseling of families. (c) 2006 Elsevier Inc. All rights reserved.