Diagnosis of 21-hydroxylase deficiency by urinary metabolite ratios using gas chromatography-mass spectrometry analysis: Reference values for neonates and infants
Diagnosis of 21-hydroxylase deficiency by urinary metabolite ratios using gas chromatography-mass spectrometry analysis: Reference values for neonates and infants
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DOI：
10.1016/j.jsbmb.2015.10.013
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发表时间：
2016-02-01
影响因子：
4.1
通讯作者：
Wudy, Stefan A.
中科院分区：
文献类型：
--
作者：
Kamrath, Clemens;Hartmann, Michaela F.;Wudy, Stefan A.
21-羟化酶缺乏症（21OHD）新生儿筛查计划的一个主要问题是假阳性结果的高比率，特别是在早产儿中。气相色谱-质谱联用（GC-MS）尿液类固醇代谢物分析适合作为一种确诊性诊断工具。本研究的目的是利用GC-MS回顾性分析新生儿和患有和不患有21OHD的婴儿的代谢物比率，重点分析糖皮质激素代谢，并为诊断21OHD提供类固醇代谢物比率的参考值。回顾性分析95例未经治疗的21OHD新生儿（1 ~ 148天）和261例未患21OHD的新生儿（100例早产儿）的尿类固醇激素代谢物的GC-MS测定结果。17 α -羟孕酮的代谢物特异性低于98%，而21-脱氧皮质醇代谢物妊娠曲酮可明显区分21OHD和非21OHD受试者。妊娠曲龙与6 α -羟基-四氢化可的松是21OHD的最佳诊断率。该比率在21OHD组的最低值（0.47）比非21OHD组的最高值（0.055）至少高出8倍。我们给出了迄今为止所描述的最大的21OHD队列中类固醇代谢物比率的适当参考值。考虑糖皮质激素代谢，特别是使用典型的新生儿6 α -羟基酸盐代谢物，可改善诊断代谢物比率。(C) 2015 Elsevier Ltd.版权所有。
One major issue of newborn screening programs for 21-hydroxylase deficiency (21OHD) is the high rate of false-positive results, especially in preterm neonates. Urinary steroid metabolite analysis using gas chromatography-mass spectrometry (GC-MS) is suitable as a confirmatory diagnostic tool.The objective of this study was to analyze retrospectively diagnostic metabolite ratios in neonates and infants with and without 21OHD using GC-MS with emphasis on glucocorticoid metabolism, and to develop reference values for the steroid metabolite ratios for the diagnosis of 21OHD.We retrospectively analyzed urinary steroid hormone metabolites determined by GC-MS of 95 untreated neonates and infants with 21OHD (1-148 days), and 261 neonates and infants (100 preterms) without 21OHD (0-217 days).Metabolites of 17 alpha-hydroxyprogesterone showed specificities below 98%, whereas the 21-deoxycortisol metabolite pregnanetriolone clearly separated 21OHD from non-21OHD subjects. The best diagnostic ratio for 21OHD was pregnanetriolone to 6 alpha-hydroxy-tetrahydrocortisone. The lowest value of this ratio in the 21OHD group (0.47) was at least eight times higher than the highest values in the non-21OHD group (0.055).We have given appropriate reference values for steroid metabolite ratios in the largest 21OHD cohort so far described. Consideration of glucocorticoid metabolism, especially the use of typical neonatal 6 alpha-hydroxylates metabolites, leads to improvement of diagnostic metabolite ratios. (C) 2015 Elsevier Ltd. All rights reserved.