{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:55:24Z","timestamp":1779245724859,"version":"3.51.4"},"reference-count":44,"publisher":"BMJ","issue":"1","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873724"],"award-info":[{"award-number":["81873724"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["19ZR1442100"],"award-info":[{"award-number":["19ZR1442100"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["20ZR1472700"],"award-info":[{"award-number":["20ZR1472700"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["22ZR1451400"],"award-info":[{"award-number":["22ZR1451400"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFC2703400"],"award-info":[{"award-number":["2022YFC2703400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Healthcare Commission Project","award":["202340103"],"award-info":[{"award-number":["202340103"]}]},{"name":"Clinical Research Center For Primary Adrenal Insufficiency, Pediatric College, Shanghai Jiao Tong University School of Medicine","award":["ELYZX202106"],"award-info":[{"award-number":["ELYZX202106"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2023,7,4]]},"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Primary adrenal insufficiency (PAI) is a rare but life-threatening condition. Differential diagnosis of numerous causes of PAI requires a thorough understanding of the condition.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To describe the genetic composition and presentations of PAI. The following data were collected retrospectively from 111 patients with non-21OHD with defined genetic diagnoses: demographic information, onset age, clinical manifestations, laboratory findings and genetic results. Patients were divided into four groups based on the underlying pathogenesis: (1) impaired steroidogenesis, (2) adrenal hypoplasia, (3) resistance to adrenocorticotropic hormone (ACTH) and (4) adrenal destruction. The age of onset was compared within the groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mutations in the following genes were identified: <jats:italic>NR0B1<\/jats:italic> (n=39), <jats:italic>STAR<\/jats:italic> (n=33), <jats:italic>CYP11B1<\/jats:italic> (n=12), <jats:italic>ABCD1<\/jats:italic> (n=8), <jats:italic>CYP17A1<\/jats:italic> (n=5), <jats:italic>HSD3B2<\/jats:italic> (n=4), <jats:italic>POR<\/jats:italic> (n=4), <jats:italic>MRAP<\/jats:italic> (n=2), <jats:italic>MC2R<\/jats:italic> (n=1), <jats:italic>CYP11A1<\/jats:italic> (n=1), <jats:italic>LIPA<\/jats:italic> (n=1) and <jats:italic>SAMD9<\/jats:italic> (n=1). Frequent clinical manifestations included hyperpigmentation (73.0%), dehydration (49.5%), vomiting (37.8%) and abnormal external genitalia (23.4%). Patients with adrenal hypoplasia typically presented manifestations earlier than those with adrenal destruction but later than those with impaired steroidogenesis (both p&lt;0.01). The elevated ACTH (92.6%) and decreased cortisol (73.5%) were the most common laboratory findings. We generated a differential diagnosis flowchart for PAI using the following clinical features: 17-hydroxyprogesterone, very-long-chain fatty acid, external genitalia, hypertension and skeletal malformation. This flowchart identified 84.8% of patients with PAI before next-generation DNA sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                     <jats:italic>STAR<\/jats:italic> and <jats:italic>NR0B1<\/jats:italic> were the most frequently mutated genes in patients with non-21OHD PAI. Age of onset and clinical characteristics were dependent on aetiology. Combining clinical features and molecular tests facilitates accurate diagnosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2022-108952","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T13:31:43Z","timestamp":1692192703000},"page":"27-35","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic and phenotypic spectrum of non-21-hydroxylase-deficiency primary adrenal insufficiency in childhood: data from 111 Chinese patients"],"prefix":"10.1136","volume":"61","author":[{"given":"Ying","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Yangpu, Shanghai, 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