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

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dc.contributor.authorBEREKET, ABDULLAH
dc.contributor.authorsGuran, Tulay; Kara, Cengiz; Yildiz, Melek; Bitkin, Eda C.; Haklar, Goncagul; Lin, Jen-Chieh; Keskin, Mehmet; Barnard, Lise; Anik, Ahmet; Catli, Gonul; Guven, Ayla; Kirel, Birgul; Tutunculer, Filiz; Onal, Hasan; Turan, Serap; Akcay, Teoman; Atay, Zeynep; Yilmaz, Gulay C.; Mamadova, Jamala; Akbarzade, Azad; Sirikci, Onder; Storbeck, Karl-Heinz; Baris, Tugba; Chung, Bon-Chu; Bereket, Abdullah
dc.date.accessioned2022-03-12T22:54:56Z
dc.date.available2022-03-12T22:54:56Z
dc.date.issued2020
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.
dc.identifier.doi10.1210/clinem/dgaa022
dc.identifier.eissn1945-7197
dc.identifier.issn0021-972X
dc.identifier.pubmed31950145
dc.identifier.urihttps://hdl.handle.net/11424/236589
dc.identifier.wosWOS:000525950100005
dc.language.isoeng
dc.publisherENDOCRINE SOC
dc.relation.ispartofJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subject3 beta HSD2 deficiency
dc.subjectCAH
dc.subjectHSD3B2
dc.subjectadrenal insufficiency
dc.subjectchildren
dc.subjectCONGENITAL ADRENAL-HYPERPLASIA
dc.subjectHSD3B2 GENE
dc.subject11-OXYGENATED ANDROGENS
dc.subjectMOLECULAR-BIOLOGY
dc.subjectMUTATION
dc.subjectTUMOR
dc.titleRevisiting Classical 3 beta-hydroxysteroid Dehydrogenase 2 Deficiency: Lessons from 31 Pediatric Cases
dc.typearticle
dspace.entity.typePublication
local.avesis.idd8f4fd98-9d48-4c23-b12e-a8c426a245f4
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.articlenumberdgaa022
local.journal.numberofpages11
local.journal.quartileQ1
oaire.citation.issue4
oaire.citation.titleJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
oaire.citation.volume105
relation.isAuthorOfPublication669e9474-4e39-453f-a4bc-4ede9cb5abac
relation.isAuthorOfPublication.latestForDiscovery669e9474-4e39-453f-a4bc-4ede9cb5abac

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