{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:41:17Z","timestamp":1791398477563,"version":"4.3.3"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>P450 side\u2010chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. The distinction between classic and nonclassic steroidogenic acute regulatory protein\u00a0deficiency has been described, whereas in SCCD is unclear. The data on gonadal function and its correlation with SCCD genotype has not been studied.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>We describe our experience and perform a systematic review of genetically proven\u00a0SCCD patients to determine the distinct phenotypic and genotypic characteristics of 46,XY SCCD\u00a0patients with typical male external genitalia (SCCD\u2010TMG) and atypical (SCCD\u2010AG) external genitalia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Patients and Measurements<\/jats:title><jats:p>Retrospective review of three genetically proven SCCD patients from our centre and per\u2010patient data analysis from a systematic review of 52 probands was performed. SCCD\u2010TMG (<jats:italic>n<\/jats:italic>\u2009=\u200919) was defined as external genitalia of Sinnecker score 1 with 46,XY \u00a0karyotype; the rest (Sinnecker 2\u20135) were classified as SCCD\u2010AG (<jats:italic>n<\/jats:italic>\u2009=\u200915).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report two new Indian cases of SCCD with three novel likely pathogenic variants and pubertal follow\u2010up of a previously reported patient. In systematic review, age at diagnosis of PAI\u00a0and elevated renin were not different between 46,XY \u00a0SCCD\u2010TMG\u00a0(<jats:italic>n<\/jats:italic>\u2009=\u200919) and SCCD\u2010AG\u00a0(<jats:italic>n<\/jats:italic>\u2009=\u200915), whereas spontaneous puberty (9\/9 vs. 0\/3, <jats:italic>p<\/jats:italic>\u2009=\u2009.0045), normal prepubertal (5\/5 vs. 6\/6, <jats:italic>p<\/jats:italic>\u2009=\u2009.002), pubertal gonadotropins (2\/9 vs. 0\/3, <jats:italic>p<\/jats:italic>\u2009=\u20091)\u00a0and normal pubertal testosterone (9\/11 vs. 0\/3, <jats:italic>p<\/jats:italic>\u2009=\u2009.027) were more common in SCCD\u2010TMG. Testicular adrenal rest tumours were exclusive to SCCD\u2010TMG (<jats:italic>n<\/jats:italic>\u2009=\u20094). SCCD\u2010TMG was associated with four particular genotypes [monoallelic p.Glu314Lys with another deleterious variant on the second allele (p.Glu314Lys\/X\u2010CHS: X\u2010compound heterozygous state), biallelic p.Arg451Trp, p.Phe215Ser\/p.Arg232Ter\u00a0and monoallelic p.Val79Ile]. 46,XX SCCD\u00a0\u00a0patients with p.Glu314Lys\/X\u2010CHS\u00a0also had normal gonadotropins with spontaneous puberty.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SCCD\u2010TMG is associated with four specific genotypes and distinct gonadal characteristics from SCCD\u2010AG with overlapping features of PAI.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14848","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T03:20:23Z","timestamp":1668136823000},"page":"351-362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Side\u2010chain cleavage enzyme deficiency: Systematic review and case series"],"prefix":"10.1111","volume":"98","author":[{"given":"Aditya","family":"Phadte","sequence":"first","affiliation":[{"name":"Department of Endocrinology Seth G S Medical College &amp; 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