{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:47:34Z","timestamp":1761061654867},"reference-count":35,"publisher":"Walter de Gruyter GmbH","issue":"8","funder":[{"name":"Asia Pacific Federation of Clinical Chemistry and Laboratory Medicine project grant."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2022-0272_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The 5\u03b1-reductase-type-2 deficiency (5ARD2) is a rare autosomal recessive 46,XY disorder of sex development caused by the mutated 5\u03b1-reductase type 2 (<jats:italic>SRD5A2<\/jats:italic>) 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\u00a0year period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0272_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2019s Hospital, Hanoi Vietnam. 5\u03b1- to 5\u03b2-reduced steroid metabolite ratio, 5a-tetrahydrocortisol to tetrahydrocortisol (5\u03b1-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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0272_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Urine steroidomic profiling was conducted for 104 male controls and 25 patients between the ages of 6\u00a0months and 13\u00a0years old. Twelve of the twenty-five 5ARD2 patients agreed to undertake genetic analysis, and two mutations of the <jats:italic>SRD5A2<\/jats:italic> gene were detected in each patient, confirming the diagnosis. All patients showed a characteristically low ratio of 5\u03b1-THF\/THF. There was no overlap of 5\u03b1-THF\/THF ratio values between control and 5ARD2 groups. The ROC of 5\u03b1-THF\/THF ratio at 0.19 showed 100% sensitivity and 100% specificity for boys between 6\u00a0months and 13\u00a0years of age.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0272_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2022-0272","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T20:22:19Z","timestamp":1653337339000},"page":"1225-1233","source":"Crossref","is-referenced-by-count":2,"title":["Validation of steroid ratios for random urine by mass spectrometry to detect 5\u03b1-reductase deficiency in Vietnamese children"],"prefix":"10.1515","volume":"60","author":[{"given":"Thi Chi Mai","family":"Tran","sequence":"first","affiliation":[{"name":"Hanoi Medical University , Hanoi , Vietnam"},{"name":"National Children\u2019s Hospital , Hanoi , Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thi Ngoc Anh","family":"Tran","sequence":"additional","affiliation":[{"name":"Viet Duc University Hospital , Hanoi , Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoang Bich Nga","family":"Le","sequence":"additional","affiliation":[{"name":"Hanoi Medical University , Hanoi , Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viet Hoa","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Viet Duc University Hospital , Hanoi , Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minh Dien","family":"Tran","sequence":"additional","affiliation":[{"name":"National Children\u2019s Hospital , Hanoi , Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi Dung","family":"Vu","sequence":"additional","affiliation":[{"name":"National Children\u2019s Hospital , Hanoi , Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronda F.","family":"Greaves","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services , Murdoch Children\u2019s Research Institute , Melbourne , Australia"},{"name":"Department of Paediatrics , University of Melbourne , Parkville , VIC , Australia"},{"name":"School of Health and Biomedical Sciences , RMIT University , Parkville , VIC , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"2023033111252079553_j_cclm-2022-0272_ref_001","doi-asserted-by":"crossref","unstructured":"Honour, JW, Brook, CG. Clinical indications for the use of urinary steroid profiles in neonates and children. Ann Clin Biochem 1997;34:45\u201354. https:\/\/doi.org\/10.1177\/000456329703400107.","DOI":"10.1177\/000456329703400107"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_002","doi-asserted-by":"crossref","unstructured":"Shackleton, C. Clinical steroid mass spectrometry: a 45\u00a0year history culminating in HPLC\u2013MS\/MS becoming an essential tool for patient diagnosis. J Steroid Biochem Mol Biol 2010;121:481\u201390. https:\/\/doi.org\/10.1016\/j.jsbmb.2010.02.017.","DOI":"10.1016\/j.jsbmb.2010.02.017"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_003","doi-asserted-by":"crossref","unstructured":"Wudy, SA, Schuler, G, S\u00e1nchez-Guijo, A, Hartmann, MF. The art of measuring steroids: principles and practice of current hormonal steroid analysis. J Steroid Biochem Mol Biol 2018;179:88\u2013103. https:\/\/doi.org\/10.1016\/j.jsbmb.2017.09.003.","DOI":"10.1016\/j.jsbmb.2017.09.003"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_004","doi-asserted-by":"crossref","unstructured":"Greaves, RF, Jevalikar, G, Hewitt, JK, Zacharin, MR. A guide to understanding the steroid pathway: new insights and diagnostic implications. Clin Biochem 2014;47:5\u201315. https:\/\/doi.org\/10.1016\/j.clinbiochem.2014.07.017.","DOI":"10.1016\/j.clinbiochem.2014.07.017"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_005","doi-asserted-by":"crossref","unstructured":"Kulle, A, Krone, N, Holterhus, PM, Schuler, G, Greaves, RF, Juul, A, et al.. Steroid hormone analysis in diagnosis and treatment of DSD: position paper of EU COST Action BM 1303 \u2018DSDnet. 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Endocr Rev 1993;14:577\u201393. https:\/\/doi.org\/10.1210\/edrv-14-5-577.","DOI":"10.1210\/edrv-14-5-577"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_009","doi-asserted-by":"crossref","unstructured":"Maimoun, L, Philibert, P, Cammas, B, Audran, F, Bouchard, P, Fenichel, P, et al.. Phenotypical, biological, and molecular heterogeneity of 5alpha-reductase deficiency: an extensive international experience of 55 patients. J Clin Endocrinol Metab 2011;96:296\u2013307. https:\/\/doi.org\/10.1210\/jc.2010-1024.","DOI":"10.1210\/jc.2010-1024"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_010","doi-asserted-by":"crossref","unstructured":"Baldinotti, F, Majore, S, Fogli, A, Marrocco, G, Ghirri, P, Vuerich, M, et al.. Molecular characterization of 6 unrelated Italian patients with 5alpha-reductase type 2 deficiency. 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Int J Androl 2010;33:841\u20137. https:\/\/doi.org\/10.1111\/j.1365-2605.2009.01036.x.","DOI":"10.1111\/j.1365-2605.2009.01036.x"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_013","doi-asserted-by":"crossref","unstructured":"Perry, RJ, Novikova, E, Wallace, AM, Donaldson, MD. Pitfalls in the diagnosis of 5\u03b1-reductase type 2 deficiency during early infancy. Horm Res Paediatr 2011;75:380\u20132. https:\/\/doi.org\/10.1159\/000324646.","DOI":"10.1159\/000324646"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_014","unstructured":"Chan, AO, But, BW, Lau, GT, Lam, AL, Ng, KL, Lam, YY, et al.. Diagnosis of 5alpha-reductase 2 deficiency: a local experience. Hong Kong Med J 2009;15:130\u20135."},{"key":"2023033111252079553_j_cclm-2022-0272_ref_015","doi-asserted-by":"crossref","unstructured":"Imperato-McGinley, J, Gautier, T, Peterson, RE, Shackleton, C. The prevalence of 5 alpha-reductase deficiency in children with ambiguous genitalia in the Dominican Republic. 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Clin Endocrinol (Oxf) 2003;58:627\u201331. https:\/\/doi.org\/10.1046\/j.1365-2265.2003.01763.x.","DOI":"10.1046\/j.1365-2265.2003.01763.x"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_026","doi-asserted-by":"crossref","unstructured":"Ocal, G, Adiyaman, P, Berbero\u011flu, M, Cetinkaya, E, Akar, N, Uysal, A, et al.. Mutations of the 5alpha-steroid reductase type 2 gene in six Turkish patients from unrelated families and a large pedigree of an isolated Turkish village. J Pediatr Endocrinol Metab 2002;15:411\u201321. https:\/\/doi.org\/10.1515\/jpem.2002.15.4.411.","DOI":"10.1515\/JPEM.2002.15.4.411"},{"key":"2023033111252079553_j_cclm-2022-0272_ref_027","doi-asserted-by":"crossref","unstructured":"Skordis, N, Patsalis, PC, Bacopoulou, I, Sismani, C, Sultan, C, Lumbroso, S. 5alpha-reductase 2 gene mutations in three unrelated patients of Greek Cypriot origin: identification of an ancestral founder effect. 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