{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:11:06Z","timestamp":1769512266431,"version":"3.49.0"},"reference-count":12,"publisher":"Walter de Gruyter GmbH","issue":"1","funder":[{"DOI":"10.13039\/501100004117","name":"A.G. Leventis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004117","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2020-0245_abs_001_w2aab3b7c10b1b6b1aab1c16b1Aa\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>3\u03b2-Hydroxysteroid dehydrogenase (3\u03b2-HSD) deficiency is a rare type of congenital adrenal hyperplasia caused by recessive loss-of-function mutations in <jats:italic>HSD3B2<\/jats:italic> gene.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2020-0245_abs_002_w2aab3b7c10b1b6b1aab1c16b2Aa\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>We report an 8.5-year-old, 46XY, Roma boy with advanced adrenarche signs born to consanguineous parents. He was born at term with ambiguous genitalia. At 15\u00a0days of age, he underwent replacement therapy with hydrocortisone and fludrocortisone due to a salt wasting (SW) crisis and adrenal insufficiency. At 3.5 years, he was admitted again with SW crisis attributed to the low\u00a0\u2013 unadjusted to body surface area\u00a0\u2013 hydrocortisone dose and presented with bilateral gynecomastia and adrenarche. At 8.5 years, his bone age was four years more advanced than his chronological age and he was prepubertal, with very high testosterone levels. Gas chromatography-mass spectrometry (GC-MS) urinary steroid metabolome analysis revealed the typical steroid metabolic fingerprint of 3\u03b2-HSD deficiency. Sequencing of the <jats:italic>HSD3B2<\/jats:italic> gene identified in homozygosity the novel p.Lys36Ter nonsense mutation. Furthermore, this patient was found to be heterozygous for p.Val281Leu in the <jats:italic>CYP21A2<\/jats:italic> gene. Both parents were identified as carriers of the p.Lys36Ter in <jats:italic>HSD3B2<\/jats:italic>.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2020-0245_abs_003_w2aab3b7c10b1b6b1aab1c16b3Aa\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A novel nonsense p.Lys36Ter mutation in <jats:italic>HSD3B2<\/jats:italic> was identified in a male patient with hypospadias. 3\u03b2-HSD deficiency due to mutations in the <jats:italic>HSD3B2<\/jats:italic> gene is extremely rare and the finding of a patient with this rare type of disorders of sex development (DSD) is one of the very few reported to date. The complexity of such diseases requires a multidisciplinary team approach regarding the diagnosis and follow-up.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2020-0245","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T08:00:56Z","timestamp":1605600056000},"page":"131-136","source":"Crossref","is-referenced-by-count":10,"title":["Late diagnosis of 3\u03b2-Hydroxysteroid dehydrogenase deficiency: the pivotal role of gas chromatography-mass spectrometry urinary steroid metabolome analysis and a novel homozygous nonsense mutation in the <i>HSD3B2<\/i> gene"],"prefix":"10.1515","volume":"34","author":[{"given":"Pavlos","family":"Fanis","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Function and Therapy , The Cyprus Institute of Neurology and Genetics , Nicosia , Cyprus"},{"name":"Cyprus School of Molecular Medicine , Nicosia , Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6890-8395","authenticated-orcid":false,"given":"Vassos","family":"Neocleous","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Function and Therapy , The Cyprus Institute of Neurology and Genetics , Nicosia , Cyprus"},{"name":"Cyprus School of Molecular Medicine , Nicosia , Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantina","family":"Kosta","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Diabetes and Metabolism 3rd Department of Pediatrics , Aristotle University School of Health Sciences, Hippokration Hospital of Thessaloniki , Thessaloniki , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aristea","family":"Karipiadou","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Diabetes and Metabolism 3rd Department of Pediatrics , Aristotle University School of Health Sciences, Hippokration Hospital of Thessaloniki , Thessaloniki , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela F.","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology & Diabetology , Steroid Research & Mass Spectrometry Unit, Justus Liebig University , Giessen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan A.","family":"Wudy","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology & Diabetology , Steroid Research & Mass Spectrometry Unit, Justus Liebig University , Giessen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos","family":"Karantaglis","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Diabetes and Metabolism 3rd Department of Pediatrics , Aristotle University School of Health Sciences, Hippokration Hospital of Thessaloniki , Thessaloniki , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios T.","family":"Papadimitriou","sequence":"additional","affiliation":[{"name":"Department of Pediatric-Adolescent Endocrinology & Diabetes , Athens Medical Center , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicos","family":"Skordis","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology , Paedi Center for specialized Pediatrics , Nicosia , Cyprus"},{"name":"St George\u2019s University of London Medical School at the University of Nicosia , Nicosia , Cyprus"},{"name":"Department of Molecular Genetics, Function and Therapy , The Cyprus Institute of Neurology and Genetics , Nicosia , Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Tsikopoulos","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery , Hippokration Hospital of Thessaloniki , Thessaloniki , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonidas A.","family":"Phylactou","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Function and Therapy , The Cyprus Institute of Neurology and Genetics , Nicosia , Cyprus"},{"name":"Cyprus School of Molecular Medicine , Nicosia , Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanouil","family":"Roilides","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Diabetes and Metabolism 3rd Department of Pediatrics , Aristotle University School of Health Sciences, Hippokration Hospital of Thessaloniki , Thessaloniki , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Papagianni","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Diabetes and Metabolism 3rd Department of Pediatrics , Aristotle University School of Health Sciences, Hippokration Hospital of Thessaloniki , Thessaloniki , 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