Keulemans J L M, Sinigerska I, Garritsen V H, Huijmans J G M, Voznyi Y V, van Diggelen O P, Kleijer W J
Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.
Prenat Diagn. 2002 Nov;22(11):1016-21. doi: 10.1002/pd.457.
Prenatal diagnosis of the Hunter syndrome (mucopolysaccharidosis type II; MPS II) is preferably achieved by the assay of iduronate-2-sulphate sulphatase (IDS) in uncultured chorionic villi (CV) as this allows early (12th week), rapid (2-3 days) and reliable results. We summarize the results of 174 prenatal analyses in the past 30 years, using various methods such as radiolabelled sulphate incorporation in amniotic fluid (AF) cells, glycosaminoglycan (GAG)-electrophoresis in AF and IDS assay in CV, CV-cells, AF and AF-cells. Twenty-seven fetuses with MPS II were diagnosed after finding clearly abnormal results in pregnancies with a male fetus; very low IDS activity has also been measured in some pregnancies with a (heterozygous) female fetus, emphasizing the need to combine enzyme assay with fetal sex determination. IDS activity has until recently been assessed by a cumbersome radioactive enzyme assay. Here we describe the use of a novel fluorigenic 4-methylumbelliferyl substrate, which allows a sensitive, rapid and convenient assay of IDS activity and reliable early prenatal diagnosis. This novel IDS assay was validated in retrospective analyses of 14 CV, CV-cell, AF and AF-cell samples from affected pregnancies in addition to prospective prenatal diagnosis in eight pregnancies at risk with one MPS II-affected fetus.
亨特综合征（黏多糖贮积症II型；MPS II）的产前诊断最好通过检测未培养的绒毛膜绒毛（CV）中的艾杜糖醛酸-2-硫酸酯酶（IDS）来实现，因为这样可以在早期（第12周）获得快速（2 - 3天）且可靠的结果。我们总结了过去30年中174例产前分析的结果，采用了多种方法，如羊水（AF）细胞中放射性硫酸盐掺入、AF中的糖胺聚糖（GAG）电泳以及CV、CV细胞、AF和AF细胞中的IDS检测。在男性胎儿妊娠中发现明显异常结果后，诊断出27例患有MPS II的胎儿；在一些（杂合子）女性胎儿妊娠中也检测到非常低的IDS活性，这强调了将酶检测与胎儿性别测定相结合的必要性。直到最近，IDS活性一直通过繁琐的放射性酶检测来评估。在此，我们描述了一种新型荧光4 - 甲基伞形酮底物的使用，它可以对IDS活性进行灵敏、快速且便捷的检测，并实现可靠的早期产前诊断。除了对8例有一个MPS II患病胎儿风险的妊娠进行前瞻性产前诊断外，这种新型IDS检测方法还在对14例来自患病妊娠的CV、CV细胞、AF和AF细胞样本的回顾性分析中得到了验证。
