鉴定经典21-羟化酶缺乏症的最佳实践应包括21-脱氧皮质醇分析和适当的异构体类固醇分离。

IF 4 Q1 GENETICS & HEREDITY
Ronda F Greaves, Monish Kumar, Nazha Mawad, Alberto Francescon, Chris Le, Michele O'Connell, James Chi, James Pitt
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引用次数: 0

摘要

关于21-脱氧皮质醇(21DF)作为经典21-羟化酶缺乏症的主要决定标志物的纳入和使用,有多种报道。我们假设这可能是由于对异构类固醇的存在和色谱分离认识不足。本研究的目的是使用第二级LC-MS/MS方法,包括将异构类固醇分离为17OHP和21DF,确定21DF在筛选和诊断由经典的21-羟化酶缺乏引起的CAH方面的比较效用。对于每个婴儿样本,在含有同位素匹配的内标物的甲醇溶液中洗脱一个3.2mm干血点。数据通过单变量和受试者操作员特征分析进行询问。924个非CAH婴儿样本(中位胎龄37周,范围22至43周)和17个21-羟化酶缺乏婴儿的类固醇图谱结果。ROC曲线显示21DF对诊断典型的21-羟化酶缺乏具有最佳的敏感性和特异性,AUC=1.0。热图显示17OHP和21DF之间具有非常强的相关性(r=0.83)。我们的数据支持21DF作为由于21-羟化酶缺乏引起的CAH的有力标志物。我们建议将21DF纳入常规新生儿筛查小组,作为二级LC-MS/MS方法、后续血浆类固醇小组和外部质量保证材料的一部分。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation.

Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation.

Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation.

Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation.

There are mixed reports on the inclusion and use of 21 deoxycortisol (21DF) as the primary decision marker for classical 21-hydroxylase deficiency. We hypothesize that this may be due to insufficient recognition of the presence and chromatographic separation of isomeric steroids. The aim of this study was to determine the comparative utility of 21DF for screening and diagnosis of CAH due to classical 21-hydroxylase deficiency using a second-tier LC-MS/MS method that included the separation of isomeric steroids to 17OHP and 21DF. For each baby sample, one 3.2 mm dried blood spot was eluted in a methanolic solution containing isotopically matched internal standards. Data were interrogated by univariate and receiver operator characteristic analysis. Steroid profile results were generated for 924 non-CAH baby samples (median gestational age 37 weeks, range 22 to 43 weeks) and 17 babies with 21-hydroxylase deficiency. The ROC curves demonstrated 21DF to have the best sensitivity and specificity for the diagnosis of classical 21-hydroxylase deficiency with an AUC = 1.0. The heatmap showed the very strong correlation (r = 0.83) between 17OHP and 21DF. Our data support 21DF as a robust marker for CAH due to 21-hydroxylase deficiency. We recommend that 21DF be incorporated into routine newborn screening panels as part of the second-tier LC-MS/MS method, follow-up plasma steroid panels, and external quality assurance material.

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来源期刊
International Journal of Neonatal Screening
International Journal of Neonatal Screening Medicine-Pediatrics, Perinatology and Child Health
CiteScore
6.70
自引率
20.00%
发文量
56
审稿时长
11 weeks
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