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。

IF 5.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Didem Helvacioglu, Aylin Tugba Canbaz, Aysel Tekmenuray-Unal, Yasin Ada, Ozge Yapici, Emine Genc, Sebile Kilavuz, Busra Gurpinar Tosun, Burcu Ozturk Hismi, Tulay Guran
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引用次数: 0

摘要

背景:由ACOX1编码的过氧化物酶体脂肪酰基辅酶a氧化酶1启动并限制了超长链脂肪酸(VLCFA)的β -氧化速率。双等位基因ACOX1突变引起假性新生儿肾上腺白质营养不良(PNALD)。原发性肾上腺功能不全(PAI)在34例PNALD患者中尚未明确表征。目的:分析1例PNALD患者及其表兄的PAI特征。方法:记录临床资料,利用下一代测序(NGS)板和750K芯片研究分子病因。血浆类固醇和VLCFAs通过质谱测定。结果:1例女性患者,年龄1.5岁,因色素沉着、低血糖、低钠血症和高钾血症进行PAI评估。她有严重的新生儿性张力减退、癫痫发作、精神运动/发育迟缓和神经功能减退的病史。分子研究显示ACOX1基因的13和14外显子的纯合缺失。生化分析显示饱和VLCFA积累。头颅磁共振成像显示双侧半颞叶中央、基底节区、脑干及小脑白质T2高强度区。高血浆ACTH,低皮质醇和类固醇前体以及高血浆肾素活性与先天性肾上腺增生(非cah)以外的PAI相容。腹部电脑断层显示双侧肾上腺萎缩。PNALD患者的表兄在7个月大时出现非cah PAI。结论:肾上腺功能不全应纳入过氧化物酶体疾病的表型谱。脂肪酰基辅酶a氧化酶1缺乏可能是非cah PAI的过氧化物酶体病因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
European Journal of Endocrinology
European Journal of Endocrinology 医学-内分泌学与代谢
CiteScore
9.80
自引率
3.40%
发文量
354
审稿时长
1 months
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.
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