{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:02:18Z","timestamp":1785265338157,"version":"3.55.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Harderoporphyria arises from biallelic CPOX gene mutations, leading to coproporphyrinogen oxidase deficiency in the inner mitochondrial membrane. The impact of CPOX gene mutations on adrenal function remains poorly understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Characterizing primary adrenal insufficiency (PAI) in 2 siblings with harderoporphyria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Clinical data were recorded, and genetic analysis was performed by whole genome sequencing (WGS). Plasma steroids and urinary porphyrins were measured by liquid chromatography-mass spectrometry and high-performance liquid chromatography, respectively. Mitochondrial function was assessed using the mitochondrial membrane potential (MMP) assay in peripheral blood mononuclear cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Patients were diagnosed with PAI at 4.5 years (P1, 46,XY) and 7 months (P2, 46,XX). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. WGS revealed a homozygous c.83_85del, p.S28* variant in CPOX. Oxidative damage to mitochondria was shown by decreased MMP in patients compared with controls (P &amp;lt; .0001). Hormonal assessment indicated severe PAI, suggestive of combined CYP11A1 and CYP11B1 deficiency.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>CPOX gene mutations cause a mixed model of PAI, affecting mitochondrial steroidogenic enzymes. Clinical manifestations of harderoporphyria may overlap with PAI signs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf089","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T08:13:30Z","timestamp":1745914410000},"page":"K31-K37","source":"Crossref","is-referenced-by-count":6,"title":["Primary adrenal insufficiency in patients with <i>CPOX<\/i> gene mutations"],"prefix":"10.1093","volume":"192","author":[{"given":"Elif","family":"Kelestemur","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine , Ba\u015f\u0131b\u00fcy\u00fck, Istanbul 34854 ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat Hakki","family":"Yarar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics, University of Health Sciences, Umraniye Research and Training Hospital , Istanbul 34764 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