{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:54Z","timestamp":1784557074526,"version":"3.55.0"},"reference-count":25,"publisher":"Bioscientifica","issue":"3","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"\n Summary<\/jats:title>\n \n Congenital adrenal hyperplasia (CAH) is one of the most common inherited rare endocrine disorders. This case report presents two female siblings with delayed diagnosis of non-classical CAH 3\n \u03b2<\/jats:italic>\n -hydroxysteroid dehydrogenase type 2 (3\n \u03b2<\/jats:italic>\n HSD2D\/\n HSD3B2<\/jats:italic>\n ) despite early hospital admission and apparent CAH manifestations such as infections, hirsutism, menstrual disturbances, and PCOS phenotype. Initially, sister 1 was misdiagnosed with PCOS and then 11-hydroxylase deficiency (\n CYP11B1<\/jats:italic>\n ), based on ultrasound, biochemical findings, and negative genetic testing for 21-hydroxylase deficiency (\n CYP21A2<\/jats:italic>\n ). Additional diagnostic workup was performed when sister 2also presented with symptoms of androgen excess\n .<\/jats:italic>\n Genetic testing for CAH\/steroid disorders finally revealed that both siblings were compound heterozygous for two variants in the\n HSD3B2<\/jats:italic>\n gene: a frameshift variant, c.558dup, p.(Thr187Hisfs*17) and a novel missense variant, c.65T>C, p.(Leu22Ser). A Synacthen test showed an insufficient cortisol increase.\n In vitro<\/jats:italic>\n studies of the variants in a cell model revealed loss of function for the p.(Thr187Hisfs*17) and partial activity for p.(Leu22Ser) confirming non-classic CAH. Overlapping symptomatology and lack of specialized knowledge on steroid biosynthesis and associated rarest forms of CAH may explain the delayed diagnosis. However, with newer diagnostic methods comprising a less biased approach, very rare forms of non-classical CAH may no longer be overlooked in the future.\n <\/jats:p>\n <\/jats:sec>\n \n Learning points<\/jats:title>\n \n \n \n Non-classic 3\n \u03b2<\/jats:italic>\n HSD2 is likely underdiagnosed.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Late diagnosis of mild non-classic 3\n \u03b2<\/jats:italic>\n HSD2 does occur and one should be aware of this diagnosis.\n <\/jats:p>\n <\/jats:list-item>\n \n Early diagnosis of NCCAH may prevent many consequences such as severe hirsutism, prolonged menstrual irregularities, infertility, or even adrenal crisis with severe infections.<\/jats:p>\n <\/jats:list-item>\n \n Comprehensive steroid profiling and genetic testing should be used earlier, especially when in doubt about a diagnosis.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-23-0090","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T07:31:34Z","timestamp":1722497494000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":4,"title":["Late diagnosis of partial 3\u03b2-hydroxysteroid dehydrogenase type 2 deficiency \u2013 characterization of a new genetic variant"],"prefix":"10.1530","volume":"2024","author":[{"given":"Cagla Margit","family":"\u00d8zdemir","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Aarhus University Hospital, Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette M\u00f8lby","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jani","family":"Liimatta","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Bern University Hospital, University of Bern, Switzerland"},{"name":"Department of Biomedical Research, University of Bern, Switzerland"},{"name":"Kuopio Pediatric Research Unit (KuPRu), University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa D","family":"Voegel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, University of Bern, Switzerland"},{"name":"Department of Nephrology, Bern University Hospital, University of Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawda Naamneh","family":"Elzenaty","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Bern University Hospital, University of Bern, Switzerland"},{"name":"Department of Biomedical Research, University of Bern, Switzerland"},{"name":"Graduate School of Cellular and Biomedical Sciences, University of Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor S","family":"Wasehuus","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Aarhus University Hospital, Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Lind-Holst","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Odense University Hospital, Odense, Denmark"},{"name":"Department of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Juul","family":"Ornstrup","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Aarhus University Hospital, Aarhus N, Denmark"},{"name":"Department of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine Bj\u00f8rn","family":"Gram","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian Bomme","family":"Ousager","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa E","family":"Fl\u00fcck","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Bern University Hospital, University of Bern, Switzerland"},{"name":"Department of Biomedical Research, University of Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5924-1720","authenticated-orcid":true,"given":"Claus H","family":"Gravholt","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Aarhus University Hospital, Aarhus N, Denmark"},{"name":"Department of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital, Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Endocrine Reviews","first-page":"91","article-title":"Congenital adrenal hyperplasia-current insights in pathophysiology, diagnostics, and management","volume":"43","author":"Claahsen-van der Grinten","year":"2022","unstructured":"Claahsen-van der Grinten HLSpeiser PWAhmed SFArlt WAuchus RJFalhammar 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