{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T08:25:06Z","timestamp":1761899106350,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>NR0B1 (DAX-1) is an orphan nuclear receptor essential for the development and regulation of the adrenal glands and gonads. Pathogenic variants in NR0B1 cause X-linked adrenal hypoplasia congenita (AHC), which typically presents with adrenal insufficiency and hypogonadotropic hypogonadism (HH) in boys. Delayed diagnosis during adolescence is uncommon but, when it occurs, can lead to preventable adrenal crisis, underscoring the need for early recognition of atypical presentations. We describe a 14-year-old boy who presented with adrenal insufficiency and delayed puberty. Genetic testing revealed a novel hemizygous in-frame duplication variant of NR0B1 (NM_000475.4:c.833_835dup p.(Leu278dup)). This variant has not been previously reported in association with X-linked AHC. The patient received hydrocortisone (10\u201312 mg\/m2\/day) and fludrocortisone (0.1 mg\/day) as replacement therapy for adrenal insufficiency, along with testosterone supplementation (100\u2013240 mg\/day) to induce pubertal progression. Plasma ACTH levels gradually decreased from 10,175 pg\/mL at diagnosis to 215 pg\/mL during follow-up, accompanied by clinical improvement in skin pigmentation and pubertal development. This case underscores the importance of NR0B1 genetic testing in children with adrenal insufficiency and HH. Early recognition and genetic confirmation are critical for appropriate management and genetic counseling. Identification of novel variants expands the NR0B1 mutational spectrum and enhances our understanding of genotype\u2013phenotype correlations in X-linked AHC.<\/jats:p>","DOI":"10.3390\/children12111469","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:29:42Z","timestamp":1761895782000},"page":"1469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Delayed Diagnosis of X-Linked Adrenal Hypoplasia Congenita in a Boy with a Novel NR0B1 Variant: A Case Report"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8405-5417","authenticated-orcid":false,"given":"Shin-Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Incheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoung Soon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Bucheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4086","DOI":"10.1210\/jc.2009-0923","article-title":"X-linked congenital adrenal hypoplasia with hypogonadotropic hypogonadism caused by an inversion disrupting a conserved noncoding element upstream of the NR0B1 (DAX1) gene","volume":"94","author":"Skinningsrud","year":"2009","journal-title":"J. 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