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致命遗传病的特异血液生物标记物

By LabMedica International staff writers
Posted on 23 Jan 2011
一种简单的血液检验有助于诊断罕见的进行性神经退化性疾病C1型尼曼-皮克(NPC1)病。

NPC1病的特征是胆固醇在内溶酶体内的积累,通过测量血浆中的这些代谢产物,可对该病做出确诊。内溶酶体是发生内吞作用时内体和溶酶体融合的产物。

华盛顿大学医学院(St. More...
Louis, MO, USA; www.medicine.wustl.edu)开展的一项合作研究评估了人血浆和组织中以及动物模型体内这种氧化胆固醇的水平。

所有接受调查的NPC1病患者血浆内非酶促胆固醇氧化产物的水平都有上升,且形成了NPC1病特异的氧甾酮曲线。氧甾酮曲线也与发病年龄和疾病的严重程度相关。他们进一步用NPC1猫模型表明,一种成熟的介入治疗能降低血浆氧甾酮标记物的水平。氧甾酮曲线通过气相色谱和质谱(GC/MS)技术得到。

虽然科学家筛查的人群中没有一组这两种关键标记物的水平比NPC患者高,但NPC患者父母和子女的标记物水平也相当高。很多家庭成员有一个突变的NPC基因,并且是该病的携带者。NPC患者有两种氧化胆固醇的水平是正常值的9-10倍。健康儿童和成人或高胆固醇、心脏病、糖尿病或患其它溶酶体存储障碍的人群这两种氧化胆固醇的水平并无升高。

NPC一般在儿童时期表现出来,它的症状很多,包括行走困难、吐字不清以及吞咽困难。到了晚期,它使病人失去行动能力,引起癫痫、痴呆以及死亡。NPC属于一种遗传病,称为lysosomal storage disorders. 这种病破坏细胞处理胆固醇的正常模式,致其在溶酶体内积累;溶酶体是一种细胞器,含有分解废物和细胞碎片的酸性水解酶。

资深作者之一Daniel S. Ory博士说:"这是一项重大进步,因为它使确诊变得容易很多,并能使我们快速评估实验性疗法的有效性。”

该研究论文发表于2010年11月3日的《科学与转化医学》杂志(Science Translational Medicine)。

Related Links:
Washington University School of Medicine >>> www.medicine.wustl.edu

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