{"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":1790874532870,"version":"4.1.0"},"reference-count":19,"publisher":"S. Karger AG","issue":"7-8","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2020]]},"abstract":"<b><i>Objective:<\/i><\/b> The objective of this study was to report CYB5A deficiency, to discuss the contribution of steroid metabolomics to diagnosis and interpretation, and to highlight the presence of testicular microlithiasis. <b><i>Methods:<\/i><\/b> Two siblings with ambiguous genitalia at birth were later found to carry novel <i>CYB5A<\/i> variants, with resulting isolated 17, 20 lyase deficiency. We compared urine steroid data obtained between birth and adulthood with that from other cases. <b><i>Results:<\/i><\/b> Neonatal urine steroid profiles show a relative increase of 16-hydroxylated pregnenolone metabolites. Thereafter, there are no distinguishing features until puberty, when sex steroid deficiency drives gonadotrophin production, resulting in marked increases of 17-hydroxyprogesterone metabolites derived from the gonads. This excess may be revealed pre-pubertally by gonadotrophin stimulation testing. Novel findings are first, a considerable capacity for DHEA synthesis in the neonatal period compared to childhood and adulthood, suggesting that DHEAS production is much less dependent on CYB5A at birth; second, no consistent change in \u201cbackdoor pathway\u201d intermediates; third, side chain cleavage of cortisol is largely unaffected, supporting the existence of a different lyase not dependent on CYB5A; fourth, increased 17-hydroxyprogesterone metabolites and very low androgen metabolites are diagnostic post-pubertally. <b><i>Conclusion:<\/i><\/b> This is the fourth disease-causing variant in <i>CYB5A<\/i> in isolated 17, 20 lyase deficiency and the first associated with testicular microlithiasis. Establishing a biochemical diagnosis pre-pubertally should now be possible using urine steroid profiling, supported by synacthen and gonadotrophin stimulation testing. We recommend liquid chromatography-mass spectrometry\/mass spectrometry rather than immunoassay for serum steroid analysis, early methaemoglobin measurement and surveillance should testicular microlithiasis be detected. <\/jats:p>","DOI":"10.1159\/000512372","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T17:16:58Z","timestamp":1616519818000},"page":"483-496","source":"Crossref","is-referenced-by-count":8,"title":["Isolated 17, 20 Lyase Deficiency Secondary to a Novel CYB5A Variant: Comparison of Steroid Metabolomic Findings with Published Cases Provides Diagnostic Guidelines and Greater Insight into Its Biological Role"],"prefix":"10.1159","volume":"93","author":[{"given":"Meera","family":"Shaunak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman F.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-6320","authenticated-orcid":false,"given":"Justin H.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0010-8"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2161"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/ng1097-201"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307586200"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0051"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2413"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1745"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0578-1310.2016.08.014"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvz016"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-616-0_17"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2017.277624"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1081\/erc-200043621"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.11.020"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.6b00532"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414673200"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/s0960-0760(01)00171-6"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1906623116"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2011.1"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.13130394"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/512372","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/512372","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:16:40Z","timestamp":1745425000000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000512372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":19,"journal-issue":{"issue":"7-8","published-online":{"date-parts":[[2021,3,15]]},"published-print":{"date-parts":[[2021,3,22]]}},"URL":"https:\/\/doi.org\/10.1159\/000512372","archive":["Portico"],"relation":{},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020]]}}}