Revisiting Classical 3?-hydroxysteroid Dehydrogenase 2 Deficiency: Lessons from 31 Pediatric Cases

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dc.authoridONAL, HASAN/0000-0001-9676-7086
dc.authoridcan yılmaz, gülay/0000-0003-0525-1231
dc.authoridYıldız, Melek/0000-0002-6603-2983
dc.authoridKara, Cengiz/0000-0002-8989-560X
dc.authoridcelebi bitkin, eda/0000-0002-6586-7305
dc.authoridGÜVEN, AYLA/0000-0002-2026-1326
dc.authoridbereket, abdullah/0000-0002-6584-9043
dc.authorwosidONAL, HASAN/GXF-4493-2022
dc.authorwosidcan yılmaz, gülay/V-1273-2018
dc.authorwosid/GMW-5030-2022
dc.authorwosidYıldız, Melek/AAT-3307-2020
dc.authorwosidŞirikçi, Önder/HGT-7114-2022
dc.authorwosidKara, Cengiz/AAI-3335-2021
dc.authorwosidcelebi bitkin, eda/GWM-8813-2022
dc.contributor.authorGuran, Tulay
dc.contributor.authorKara, Cengiz
dc.contributor.authorYildiz, Melek
dc.contributor.authorBitkin, Eda C.
dc.contributor.authorHaklar, Goncagul
dc.contributor.authorLin, Jen-Chieh
dc.contributor.authorKeskin, Mehmet
dc.date.accessioned2024-06-12T15:23:13Z
dc.date.available2024-06-12T15:23:13Z
dc.date.issued2020
dc.departmentTrakya Üniversitesien_US
dc.description.abstractContext: The clinical effects of classical 3 beta-hydroxysteroid dehydrogenase 2 (3 beta HSD2) deficiency are insufficiently defined due to a limited number of published cases. Objective: To evaluate an integrated steroid metabolome and the short- and long-term clinical features of 3 beta HSD2 deficiency. Design: Multicenter, cross-sectional study. Setting: Nine tertiary pediatric endocrinology clinics across Turkey. Patients: Children with clinical diagnosis of 3 beta HSD2 deficiency. Main Outcome Measures: Clinical manifestations, genotype-phenotype-metabolomic relations. A structured questionnaire was used to evaluate the data of patients with clinical 3 beta HSD2 deficiency. Genetic analysis of HSD3B2 was performed using Sanger sequencing. Novel HSD3B2 mutations were studied in vitro. Nineteen plasma adrenal steroids were measured using LC-MS/MS. Results: Eleven homozygous HSD3B2 mutations (6 novel) were identified in 31 children (19 male/12 female; mean age: 6.6 +/- 5.1 yrs). The patients with homozygous pathogenic HSD3B2 missense variants of > 5% of wild type 3 beta HSD2 activity in vitro had a non-salt-losing clinical phenotype. Ambiguous genitalia was an invariable feature of all genetic males, whereas only 1 of 12 female patients presented with virilized genitalia. Premature pubarche was observed in 78% of patients. In adolescence, menstrual irregularities and polycystic ovaries in females and adrenal rest tumors and gonadal failure in males were observed. Conclusions: Genetically-documented 3 beta HSD2 deficiency includes salt-losing and non-salt-losing clinical phenotypes. Spared mineralocorticoid function and unvirilized genitalia in females may lead to misdiagnosis and underestimation of the frequency of 3 beta HSD2 deficiency. High baseline 17OHPreg to cortisol ratio and low 11-oxyandrogen concentrations by LC-MS/MS unequivocally identifies patients with 3 beta HSD2 deficiency.en_US
dc.description.sponsorshipMedical Research Council of Marmara University [SAG-C-TUP-131216-0528]en_US
dc.description.sponsorshipThis work has been supported by the Medical Research Council of Marmara University(Project Grant SAG-C-TUP-131216-0528 to TG).en_US
dc.identifier.doi10.1210/clinem/dgaa022
dc.identifier.issn0021-972X
dc.identifier.issn1945-7197
dc.identifier.issue4en_US
dc.identifier.pmid31950145en_US
dc.identifier.scopus2-s2.0-85081145912en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1210/clinem/dgaa022
dc.identifier.urihttps://hdl.handle.net/20.500.14551/17899
dc.identifier.volume105en_US
dc.identifier.wosWOS:000525950100005en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherEndocrine Socen_US
dc.relation.ispartofJournal Of Clinical Endocrinology & Metabolismen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject3 Beta HSD2 Deficiencyen_US
dc.subjectCAHen_US
dc.subjectHSD3B2en_US
dc.subjectAdrenal Insufficiencyen_US
dc.subjectChildrenen_US
dc.subjectCongenital Adrenal-Hyperplasiaen_US
dc.subjectHsd3b2 Geneen_US
dc.subject11-Oxygenated Androgensen_US
dc.subjectMolecular-Biologyen_US
dc.subjectMutationen_US
dc.subjectTumoren_US
dc.titleRevisiting Classical 3?-hydroxysteroid Dehydrogenase 2 Deficiency: Lessons from 31 Pediatric Casesen_US
dc.typeArticleen_US

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