{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T18:25:05Z","timestamp":1763749505867,"version":"3.41.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"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>Peroxisomal fatty acyl-CoA oxidase 1, encoded by ACOX1, initiates and limits the rate of beta-oxidation of very long-chain fatty acids (VLCFA). Biallelic ACOX1 mutations cause pseudo-neonatal adrenoleukodystrophy (PNALD). Primary adrenal insufficiency (PAI) has not been clearly characterized in the 34 PNALD patients reported to date.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Characterizing PAI in a patient and her cousin with PNALD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Clinical data were recorded, and molecular etiologies were investigated using next-generation sequencing panels and 750K microarray. Plasma steroids and VLCFAs were measured via mass spectrometry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A 1.5-year-old female patient was evaluated for PAI due to hyperpigmentation, hypoglycemia, hyponatremia and hyperkalemia. She had a history of severe neonatal-onset hypotonia, seizures, psychomotor\/developmental delay, and neurological regression. Molecular studies revealed a homozygous deletion encompassing exons 13 and 14 of the ACOX1 gene. Biochemical analysis revealed accumulation of saturated VLCFA. Cranial magnetic resonance imaging showed T2 high-intensity areas in bilateral centrum semiovale, basal ganglia, brainstem and cerebellar white matter. High plasma ACTH, low cortisol and steroid precursors along with high plasma renin activity were compatible with a PAI other than congenital adrenal hyperplasia (non-CAH). Abdominal computerized tomography demonstrated bilateral adrenal atrophy. The cousin of the patient with PNALD developed non-CAH PAI at 7 months of age.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Adrenal insufficiency should be considered in the phenotypic spectrum of peroxisomal disorders. Fatty acyl-CoA oxidase 1 deficiency may emerge as a peroxisomal etiology of non-CAH PAI.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf094","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T12:56:57Z","timestamp":1746536217000},"page":"K38-K43","source":"Crossref","is-referenced-by-count":1,"title":["Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic <i>ACOX1<\/i> mutations"],"prefix":"10.1093","volume":"192","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8687-6326","authenticated-orcid":false,"given":"Didem","family":"Helvacioglu","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology, School of Medicine, Marmara University , Istanbul 34854 ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aylin Tugba","family":"Canbaz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, School 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