Newborn screening for X-linked adrenoleukodystrophy (X-ALD): Validation of a combined liquid chromatography-tandem mass spectrometric (LC-MS/MS) method
Newborn screening for X-linked adrenoleukodystrophy (X-ALD): Validation of a combined liquid chromatography-tandem mass spectrometric (LC-MS/MS) method
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DOI：
10.1016/j.ymgme.2009.03.010
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发表时间：
2009-07-01
影响因子：
3.8
通讯作者：
Raymond, Gerald V.
中科院分区：
文献类型：
--
作者：
Hubbard, Walter C.;Moser, Ann B.;Raymond, Gerald V.
由于缺乏公认的标准方法，新生儿x -连锁肾上腺脑白质营养不良（X-ALD）筛查到目前为止在实施上受到限制。我们之前报道了一种使用LC-MS/MS分析的技术，可以为新生儿筛查X-ALD提供基础。诊断X-ALD和其他过氧化物酶体β -氧化的过氧化物酶体疾病的目标分析物是1-己糖烷酰-2-lyso-sn-3-甘油-磷酸胆碱（26:0-lyso-PC）。我们在这里报告了使用目标化合物的真实标准的分析方法的验证。该方法柱上注射灵敏度< 1.0 fmol，相关系数R(2)为0.9987。26:0-lyso-PC的四氘模拟作为内部标准。该临床方法的敏感性通过从国家新生儿筛查项目中检索的17例过氧化物酶体疾病新生儿样本得到证实。这些样本与1000多个新生儿样本一起运行。所有受影响的个体都被识别出来，只有一个例外。一个样本作为受影响的样本没有X-ALD的生化或遗传异常，因此被认为是样本身份的错误。这些研究清楚地表明，该方法在识别过氧化物酶体p氧化缺陷（如X-ALD）个体方面具有高度敏感性和准确性。(C) 2009爱思唯尔公司所有航班预订。
Newborn screening for X-linked adrenoleukodystrophy (X-ALD) has until now been limited in implementation because of the lack of an accepted standard methodology. We have previously reported a technique using LC-MS/MS analysis that could provide the basis for screening of newborns for X-ALD. The target analyte diagnostic for X-ALD and other peroxisomal disorders of peroxisomal beta-oxidation is 1-hexacosanoyl-2-lyso-sn-3-glycero-phosphorylcholine (26:0-lyso-PC). We report here the validation of the analytical method using an authentic standard of the target compound. The method possesses sensitivity of < 1.0 fmole injected on column with a correlation coefficient (R(2)) of 0.9987. A tetradeuterated analog of 26:0-lyso-PC served as the internal standard. The sensitivity of this clinical method was confirmed using 17 newborn samples of individuals with peroxisomal disorders retrieved from state newborn screening programs. These samples were run masked with over 1000 newborn samples. All affected individuals were identified with one exception. One sample which was retrieved as an affected did not have the biochemical or genetic abnormality of X-ALD and thus is considered an error in sample identity. These studies clearly show that the method is highly sensitive and accurate in identifying individuals with a defect in peroxisomal p-oxidation such as X-ALD. (C) 2009 Elsevier Inc. All fights reserved.