{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:05:00Z","timestamp":1758845100525,"version":"3.44.0"},"reference-count":98,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Congenital adrenal hyperplasia (CAH) due to 3\u03b2-hydroxysteroid dehydrogenase type 2 deficiency (3\u03b2-HSD2D) is an exceptionally rare disorder affecting adrenal steroidogenesis, leading to variable clinical presentations. This study aims to highlight the phenotypic variability and management challenges associated with 3\u03b2-HSD2D through the analysis of three pediatric cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively reviewed three patients diagnosed with 3\u03b2-HSD2D at the Pediatric Endocrinology Department of the University Children\u2019s Hospital in Krakow. Clinical features, laboratory findings, genetic analyses, and management strategies were evaluated. A detailed literature overview has been performed to find previously described 3\u03b2-HSD2D patients and correlate clinical presentation with distinct variants in the <jats:italic>HSD3B2<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Case 1: A female neonate presented with adrenal insufficiency, electrolyte imbalances, hyperpigmentation, and congenital heart defects. Genetic testing revealed a homozygous missense pathogenic variant c.760T&amp;gt;G (p.Tyr254Asp) in the <jats:italic>HSD3B2<\/jats:italic> gene. Hydrocortisone and fludrocortisone therapy was introduced in the 2nd week of life. Case 2: A male infant exhibited atypical genitalia without salt-wasting crises. Compound heterozygous pathogenic variants c.760T&amp;gt;G (p.Tyr254Asp) and c.308-6G&amp;gt;A in <jats:italic>HSD3B2<\/jats:italic> gene were identified. He received therapy with testosterone prior to hypospadias correction and started therapy with hydrocortisone at the age of 1 y 10 m due to increased growth velocity and acceleration of bone age. Case 3: A female infant with salt-wasting crises and virilization was diagnosed with 3\u03b2-HSD2D. She additionally developed polycystic kidney disease, gallbladder stones and ovarian cysts. A pathogenic c.849del variant in homozygosity in <jats:italic>HSD3B2<\/jats:italic> was detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This work underscores the clinical heterogeneity of 3\u03b2-HSD2D and the necessity for comprehensive genetic evaluation. Variants in the <jats:italic>HSD3B2<\/jats:italic> gene contribute to diverse phenotypes, complicating diagnosis and management. Retrospective evaluation of previously described cases offers us guidelines in the management of patients, who need multidisciplinary care involving endocrinology, genetic, gynecology, and urology specialists.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1642051","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T04:18:52Z","timestamp":1758773932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic and therapeutic pitfalls in the management of pediatric patients with 3\u03b2-hydroxysteroid dehydrogenase type 2 (3\u03b2-HSD2) deficiency - a single center 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