{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:08:49Z","timestamp":1790874529836,"version":"4.1.0"},"reference-count":14,"publisher":"Walter de Gruyter GmbH","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2025-0549_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>17\u03b2-Hydroxysteroid dehydrogenase 3 (17\u03b2-HSD3) deficiency is a rare 46XY disorder of sex development (DSD) of androgen biosynthesis. We aimed to describe the complexities in diagnosis, gender assignment, and the timing of irreversible surgical interventions in 17\u03b2-HSD3 deficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0549_abs_002\">\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We described three genetically confirmed cases of 46XY DSD due to 17\u03b2-HSD3 deficiency. All of them had female-appearing external genitalia, and the third case had well-developed breasts with clitoromegaly. The biochemical evaluation showed hCG-stimulated T\/A ratios of 0.4 and 0.35 in Cases 1 and 2, respectively, and an unstimulated T\/A ratio of 0.25 in Case 3. Molecular analysis revealed three\u00a0different\n                      <jats:italic>HSD17B3<\/jats:italic>\n                      variants: c.72C&gt;A(p.Cys24Ter), c.764C&gt;T(p.Ser255Leu), and c.607-1G&gt;A(3\u2019splice site) in the respective cases. Despite the female-appearing external genitalia in Case 1, the parents decided to rear the child as male, whereas Cases 2 and 3 retained a female gender identity. The first two cases were advised to have regular follow-up for gender dysphoria, while Case 3 was managed with injectable leuprolide depot and anti-androgens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0549_abs_003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      17\u03b2-HSD3 deficiency remains a challenging 46 XY DSD due to its clinical heterogeneity and diverse molecular spectrum. This report adds to current molecular knowledge by reporting two novel variants in the\n                      <jats:italic>HSD17B3<\/jats:italic>\n                      \u00a0gene.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2025-0549","type":"journal-article","created":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T09:55:33Z","timestamp":1769334933000},"page":"303-310","source":"Crossref","is-referenced-by-count":1,"title":["Rare phenotypic spectrum of 17\u03b2-hydroxysteroid dehydrogenase 3 deficiency: case series from infancy to adolescence"],"prefix":"10.1515","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5451-0848","authenticated-orcid":false,"given":"Subbiah","family":"Sridhar","sequence":"first","affiliation":[{"name":"Department of Endocrinology , 56912 Madurai Medical College and Government Rajaji Hospital , Madurai , Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravind Kumar","family":"Muthu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , 56912 Madurai Medical College and Government Rajaji Hospital , Madurai , Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreenivasan","family":"Palaniappan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , 56912 Madurai Medical College and Government Rajaji Hospital , Madurai , Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuppusamy","family":"Nandini","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics , Madurai Medical College and Government Rajaji Hospital , Madurai , Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravindan","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery , Madurai Medical College and Government Rajaji Hospital , Madurai , Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Kalavathy","sequence":"additional","affiliation":[{"name":"Department of Pathology , Madurai Medical College and Government Rajaji Hospital , Madurai , Tamil Nadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"2026030907573170965_j_jpem-2025-0549_ref_001","doi-asserted-by":"crossref","unstructured":"Krishnappa, B, Arya, S, Lila, AR, Sarathi, V, Memon, SS, Barnabas, R, et al.. 17\u03b2 hydroxysteroid dehydrogenase 3 deficiency in 46,XY disorders of sex development: our experience and a gender role-focused systematic review. Clin Endocrinol 2022;97:43\u201351. https:\/\/doi.org\/10.1111\/cen.14694.","DOI":"10.1111\/cen.14694"},{"key":"2026030907573170965_j_jpem-2025-0549_ref_002","doi-asserted-by":"crossref","unstructured":"Baidya, A, Basu, AK, Bhattacharjee, R, Biswas, D, Biswas, K, Chakraborty, PP, et al.. Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement. J\u00a0Pediatr Endocrinol Metab 2022;36:4\u201318. https:\/\/doi.org\/10.1515\/jpem-2022-0515.","DOI":"10.1515\/jpem-2022-0515"},{"key":"2026030907573170965_j_jpem-2025-0549_ref_003","doi-asserted-by":"crossref","unstructured":"George, MM, New, MI, Ten, S, Sultan, C, Bhangoo, A. The clinical and molecular heterogeneity of 17\u03b2HSD-3 enzyme deficiency. 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Clin Endocrinol 2000;53:697\u2013702. https:\/\/doi.org\/10.1046\/j.1365-2265.2000.01166.x.","DOI":"10.1046\/j.1365-2265.2000.01166.x"},{"key":"2026030907573170965_j_jpem-2025-0549_ref_008","doi-asserted-by":"crossref","unstructured":"Barnabas, R, Lila, AR, Memon, SS, Karlekar, M, Arya, S, Thakkar, K, et al.. Diagnostic accuracy of serum steroids and peptides in the evaluation of 46, XY disorders of sex development (DSD). Clin Endocrinol 2025;103:823\u201332. https:\/\/doi.org\/10.1111\/cen.70017.","DOI":"10.1111\/cen.70017"},{"key":"2026030907573170965_j_jpem-2025-0549_ref_009","doi-asserted-by":"crossref","unstructured":"Khattab, A, Yuen, T, Yau, M, Mendon\u00e7a, DE, Biharinho, B, New, MI, et al.. Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency. J\u00a0Pediatr Endocrinol Metabol 2015;28:623\u20138. https:\/\/doi.org\/10.1515\/jpem-2014-0295.","DOI":"10.1515\/jpem-2014-0295"},{"key":"2026030907573170965_j_jpem-2025-0549_ref_010","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, CI, Carri\u00e7o, J, Bastos, M, Lemos, MC. Disorder of sex development due to 17-Beta-Hydroxysteroid dehydrogenase type 3 deficiency: a case report and review of 70 different HSD17B3 mutations reported in 239 patients. Int J Mol Sci 2022;23:10026. https:\/\/doi.org\/10.3390\/ijms231710026.","DOI":"10.3390\/ijms231710026"},{"key":"2026030907573170965_j_jpem-2025-0549_ref_011","doi-asserted-by":"crossref","unstructured":"W\u00fcnsch, L, Holterhus, PM, Wessel, L, Hiort, O. Patients with disorders of sex development (DSD) at risk of gonadal tumour development: management based on laparoscopic biopsy and molecular diagnosis. 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