{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T18:11:35Z","timestamp":1763748695070,"version":"3.40.5"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Biallelic <jats:italic>QRSL1<\/jats:italic> mutations cause mitochondrial \u2018combined oxidative phosphorylation deficiency-40\u2019 (COXPD40). COXPD40 has been reported to be invariably lethal in infancy. Adrenal insufficiency was weakly reported and investigated among seven previously reported patients with COXPD40.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>We report the clinical, biochemical, molecular, and functional characteristics of a patient with adrenal insufficiency due to COXPD40.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>The medical history and adrenal function tests were examined. Genetic analysis was performed using whole-exome sequencing. Mitochondrial function was tested using mitochondrial membrane potential (MMP) and superoxide dismutase (SOD) enzyme assays.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>An 8-year-old boy was investigated for adrenal insufficiency. He also had mild developmental delay, sensorineural hearing loss, hypertrophic cardiomyopathy, nephrocalcinosis, elevated parathyroid hormone and creatine kinase, and lactic acidosis. Biallelic novel <jats:italic>QRSL1<\/jats:italic> variants (c.300T&gt;A;Y100* and c.610G&gt;A;G204R) were identified. Oxidative damage in mitochondria was shown by reduced MMP and SOD assays in the patient compared to controls (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). Adrenal function tests revealed a \u2018primary adrenal insufficiency other than congenital adrenal hyperplasia\u2019 (non-CAH PAI) with an isolated glucocorticoid deficiency. In the 8-year follow-up, having the longest survival of reported COXPD40 patients, he had preserved mineralocorticoid functions and gonadal steroidogenesis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Biallelic <jats:italic>QRSL1<\/jats:italic> mutations can cause non-CAH PAI. Adrenal functions should be monitored in mitochondrial disorders to improve clinical outcomes.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-22-0233","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T13:58:25Z","timestamp":1656338305000},"page":"K27-K32","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":6,"title":["Primary adrenal insufficiency in a patient with biallelic QRSL1 mutations"],"prefix":"10.1093","volume":"187","author":[{"given":"Fatma","family":"Dursun","sequence":"first","affiliation":[{"name":"Umraniye Training and Research Hospital, Department of Pediatric Endocrinology and Diabetes"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hulya Maras","family":"Genc","sequence":"additional","affiliation":[{"name":"Umraniye Training and Research Hospital, Department of Pediatric Neurology, University of Health Sciences, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ay\u015fe","family":"Mine Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"School of Medicine, Department of Biochemistry, Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Tas","sequence":"additional","affiliation":[{"name":"Umraniye Training and Research Hospital, Department of Pediatric Nutrition and Metabolism"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Metin","family":"Eser","sequence":"additional","affiliation":[{"name":"Umraniye Training and Research Hospital, Department of Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cemile","family":"Pehlivanoglu","sequence":"additional","affiliation":[{"name":"Umraniye Training and Research Hospital, Department of Pediatric Nephrology, University of Health Sciences, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Betul Karademir","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"School of Medicine, Department of Biochemistry, Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2658-6866","authenticated-orcid":true,"given":"Tulay","family":"Guran","sequence":"additional","affiliation":[{"name":"School of Medicine, Department of Pediatric Endocrinology and Diabetes, Marmara University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"bib1","series-title":"Nature Reviews: Endocrinology","first-page":"92","article-title":"Mitochondrial disease and endocrine dysfunction","volume":"13","author":"Chow","year":"2017","unstructured":"Chow JRahman JAchermann JCDattani MTRahman S. 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