用质谱法检测越南儿童5α-还原酶缺乏症的随机尿液类固醇比例验证

Thin-Mai T Tran, Thị Ngọc Lam Trần, Hoang Bich Nga Le, Việt Hoa Nguyễn, M. Tran, C. Vu, R. Greaves
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摘要

摘要目的5α-还原酶-2型缺乏症(5ARD2)是由5α-还原酶2型(SRD5A2)基因突变引起的一种罕见的常染色体隐性46,XY性发育疾病。在这种疾病中,睾酮转化为二氢睾酮的缺陷导致胎儿发育期间男性生殖器模糊的不同表现。我们的目的是研究4年期间出现5ARD2的患者的特征。方法随机收集越南河内市国立儿童医院2017 ~ 2021年对照组和疑似5ARD2患者尿液样本,采用气相色谱-质谱联用(GC-MS)法测定尿液甾体代谢产物,采用ROC曲线分析5α-与5β-减少的甾体代谢产物5a-四氢皮质醇/四氢皮质醇(5α-THF/THF)比值。采用气相色谱-质谱法对25例诊断为5ARD2的患者进行了分子检测。结果对104名男性对照组和25名年龄在6个月至13岁之间的患者进行了尿甾体组学分析。25例5ARD2患者中有12例同意进行遗传分析,在每位患者中检测到两个SRD5A2基因突变,证实了诊断。所有患者均表现出特征性的5α-THF/THF的低比值。对照组与5ARD2组间5α-THF/THF比值值无重叠。5α-THF/THF比值的ROC值为0.19,对6个月~ 13岁的男孩具有100%的敏感性和100%的特异性。结论气相色谱-质谱分析尿液类固醇代谢组有助于5ARD2的诊断。我们建议考虑随机尿液类固醇分析作为诊断5ARD2的一线检查。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Validation of steroid ratios for random urine by mass spectrometry to detect 5α-reductase deficiency in Vietnamese children
Abstract Objectives The 5α-reductase-type-2 deficiency (5ARD2) is a rare autosomal recessive 46,XY disorder of sex development caused by the mutated 5α-reductase type 2 (SRD5A2) gene. In this disease, defective conversion of testosterone to dihydrotestosterone leads to variable presentations of male ambiguous genitalia during fetal development. We aimed to examine characteristics of patients presenting with 5ARD2 over a 4 year period. Methods Random urine samples of control and patients with suspected 5ARD2 were collected and urine steroidomic metabolites were measured by Gas chromatography-mass spectrometry (GC-MS) in the period from 2017 to 2021 at National Children’s Hospital, Hanoi Vietnam. 5α- to 5β-reduced steroid metabolite ratio, 5a-tetrahydrocortisol to tetrahydrocortisol (5α-THF/THF), was reviewed by receive operator characteristics (ROC) curve analysis. Molecular testing was offered to 25 patients who were diagnosed with 5ARD2 by GC-MS urinary steroid analysis. Results Urine steroidomic profiling was conducted for 104 male controls and 25 patients between the ages of 6 months and 13 years old. Twelve of the twenty-five 5ARD2 patients agreed to undertake genetic analysis, and two mutations of the SRD5A2 gene were detected in each patient, confirming the diagnosis. All patients showed a characteristically low ratio of 5α-THF/THF. There was no overlap of 5α-THF/THF ratio values between control and 5ARD2 groups. The ROC of 5α-THF/THF ratio at 0.19 showed 100% sensitivity and 100% specificity for boys between 6 months and 13 years of age. Conclusions Analysis of the urine steroid metabolome by GC-MS can be used to assist in the diagnosis of 5ARD2. We recommend consideration of random urine steroid analysis as a first-line test in the diagnosis of 5ARD2.
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