{"title":"与双等位基因ACOX1突变相关的假性新生儿肾上腺白质营养不良引起的原发性肾上腺功能不全。","authors":"Didem Helvacioglu, Aylin Tugba Canbaz, Aysel Tekmenuray-Unal, Yasin Ada, Ozge Yapici, Emine Genc, Sebile Kilavuz, Busra Gurpinar Tosun, Burcu Ozturk Hismi, Tulay Guran","doi":"10.1093/ejendo/lvaf094","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>Characterizing PAI in a patient and her cousin with PNALD.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"K38-K43"},"PeriodicalIF":5.3000,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.\",\"authors\":\"Didem Helvacioglu, Aylin Tugba Canbaz, Aysel Tekmenuray-Unal, Yasin Ada, Ozge Yapici, Emine Genc, Sebile Kilavuz, Busra Gurpinar Tosun, Burcu Ozturk Hismi, Tulay Guran\",\"doi\":\"10.1093/ejendo/lvaf094\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>Characterizing PAI in a patient and her cousin with PNALD.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":11884,\"journal\":{\"name\":\"European Journal of Endocrinology\",\"volume\":\" \",\"pages\":\"K38-K43\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2025-04-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Endocrinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ejendo/lvaf094\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ejendo/lvaf094","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.
Background: 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.
Objective: Characterizing PAI in a patient and her cousin with PNALD.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍:
European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica.
The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology.
Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials.
Equal consideration is given to all manuscripts in English from any country.