{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:08:52Z","timestamp":1790874532851,"version":"4.1.0"},"reference-count":23,"publisher":"Walter de Gruyter GmbH","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2024-0613_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>17\u03b1-Hydroxylase and 17,20-lyase are enzymes encoded by the <jats:italic>CYP17A1<\/jats:italic> gene mapped at chromosome 10q, and are required for the synthesis of sex steroids and cortisol. 17\u03b1-hydroxylase deficiency causes a decrease in cortisol and androgen with a subsequent overproduction of adrenocorticotrophic hormone (ACTH), gonadotropin, and 11-deoxycorticosterone. However, isolated 17,20-lyase deficiency is a rare condition that results in sex steroid deficiency with normal serum cortisol. This case series aims to report a novel canonical splice site <jats:italic>CYB5A<\/jats:italic> variant causing isolated 17,20-lyase deficiency and highlight the utility of steroid metabolomics in diagnosing 17\u03b1-hydroxylase and isolated 17,20-lyase deficiencies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2024-0613_abs_002\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>We describe four patients with ambiguous genitalia who were accurately diagnosed through steroid metabolomics using liquid chromatography- mass spectroscopy (LC-MS). Genetic testing identified a novel homozygous likely pathogenic 5\u2032 canonical splice site variant, c.129\u00a0+\u00a01G&gt;A in intron 1 of <jats:italic>CYB5A<\/jats:italic> gene, resulting in isolated 17, 20 lyase deficiency.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2024-0613_abs_003\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Here, we report four patients with 46, XY disorder of sexual development (DSD) from two families with 17\u03b1-hydroxylase deficiency and isolated 17,20-lyase deficiency due to cytochrome b5 variant with a variable spectrum of under-virilization who had received inadequate treatment for a prolonged period of time due to incorrect diagnosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2024-0613","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T06:01:17Z","timestamp":1742796077000},"page":"649-657","source":"Crossref","is-referenced-by-count":4,"title":["Two families, two pathways: a case series of 46, XY DSD with 17\u03b1-hydroxylase deficiency and isolated 17,20-lyase deficiency due to novel <i>CYB5A<\/i> variant"],"prefix":"10.1515","volume":"38","author":[{"given":"Rakesh","family":"Garg","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism , AIIMS Delhi , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manasvini","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism , AIIMS Delhi , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh Kumar","family":"Arya","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism , AIIMS Delhi , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viveka P.","family":"Jyotsna","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism , AIIMS Delhi , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Khadgawat","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism , AIIMS Delhi , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"2025053006390459680_j_jpem-2024-0613_ref_001","doi-asserted-by":"crossref","unstructured":"Krone, N, Arlt, W. 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