黏多糖贮积症Ⅱ型的诊断与产前诊断  

Postnatal and prenatal diagnosis of mucopolysaccharidosis type Ⅱ(Hunter syndrome)

作　　者：张为民[1] 施惠平[1] 李贝特[1] 赵时敏[2] 戚庆炜[1] 孙念怙[1] 黄尚志[3] 

机构地区：[1]中国医学科学院基础医学研究所 [2]北京协和医院儿科 [3]北京协和医院妇产科

出　　处：《中华儿科杂志》2006年第9期644-647,共4页Chinese Journal of Pediatrics

基　　金："十五"国家科技攻关计划课题经费资助(2004BA720A04)

摘　　要：目的建立用荧光底物测定艾杜糖-2-硫酸酯酶(IDS)活性的方法,应用该方法对黏多糖贮积症Ⅱ型(MPSⅡ)病例进行临床鉴别诊断,对高危妊娠的孕妇进行产前诊断。方法采用人工合成的荧光底物4-甲基伞形酮-α-艾杜糖苷-2-硫酸,测定 MPSⅡ疑似患儿血浆中 IDS 活性,并用绒毛或经培养的羊水细胞为检材,对高危妊娠的孕妇进行产前诊断。同时观察孕妇血浆 IDS 活性变化,用基因诊断方法检测胎儿性别。结果获得中国正常人 IDS 活性正常值:血浆中为240.2～668.2nmol/(4 h·ml),绒毛组织为37.2～54.9 nmol/(4 h·mg 蛋白),经培养的羊水细胞为21.4～74.4nmol/(4 h·mg 蛋白);患者血浆的 IDS 活性为0.3～18.6 nmol/(4 h·ml),肯定杂合子的血浆酶活性为88.7～547.9 nmol/(4 h·ml)。在50例疑似患儿中确诊了46例 MPSⅡ患者。10例产前诊断中检出4例男性胎儿患病,5例为女性胎儿。结论荧光法测定 IDS 活性是敏感、可靠、快速的方法,可用于病例鉴别诊断及孕早期 MPSⅡ高危妊娠的产前诊断。Objective Mucopolysaccharidosis type Ⅱ （ MPS Ⅱ ,Hunter syndrome,OMIM 309900） is an X-linked recessive lysosomal storage disease resulting from a deficiency of iduronte-2-sulphate sulphatase （IDS）. The present study aimed to establish an enzyme assay method for IDS activity for carrying out postnatal and prenatal diagnosis of MPS Ⅱ by means of IDS activity assay on plasma, uncultured chorionic villi （CV） and cultured amniotic fluid cells （AF cell） using a new synthesized substrate. Methods A fluorigenic substrate （4-methylumbelliferyl-α-iduronate-2-sulphate, MU-α-Idu-2S）was used for the assay of IDS activity. IDS activity in plasma was determined for diagnosis of the proband. Prenatal diagnosis in l0 pregnancies at risk was carried out according to IDS activity on uncultured CV at llth week or on cultured AF cell at 18th week of gestation. At the same time, IDS activity was also determined in the maternal plasmas to observe the change of IDS activity in pregnancy. The fetal sex determination was performed by PCR amplification of the ZFX/ZFY genes. Result The IDS activity in plasma of normal controls and obligate heterozygotes were 240.2 - 668.2 nmol/（4 h · ml） and 88.7 - 547.9 nmol/（4 h · ml）, respectively, while the enzyme activities in plasmas were in the range of 0. 3 - 18. 6 nmol/（4 h · ml） in affected male. The IDS activities were 37. 2 -54. 9 nmol/（4 h · mg protein） and 21.4 -74. 4 nmol/（4 h · mg protein） in CV and cultured AF cells respectively. Out of 50 suspected cases, 46 were diagnosed as having MPS Ⅱ and 4 were excluded. Prenatal diagnosis was performed on 10 pregnancies at risk. Four of 5 male fetuses[IDS activity were 4.7, 1. 8, 7.0 nmol/（4h · mg protein） in CV, 0. 6 nmol/（4 h · mg protein） in AF celll were diagnosed as having MPS Ⅱ and the other 5 fetuses were normal females[ IDS activity were： 48. 7, 5. 9, 25. 2 nmol/（4 h · mg protein） in CV, 55.2, 40. 9 nmol/（4 h · mg protein） in AF cell]. Increased IDS activity was obs

关 键 词：黏多糖累积病Ⅱ型 艾杜糖醛酸硫酸酯酶 产前诊断 

分 类 号：R725.8[医药卫生—儿科] R714.5[医药卫生—临床医学]