The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA genes. In line with this, isolated cases of known monogenic disorders, and also, new genetic diseases, which present with abnormal brain iron phenotypes compatible with NBIA, have been described. Several pathways are involved in NBIA syndromes: iron and lipid metabolism, mitochondrial dynamics, and autophagy. However, many neurodegenerative conditions share features such as mitochondrial dysfunction and oxidative stress, given the bioenergetics requirements of neurons. This review aims to describe the existing link between the classical ten NBIA forms by examining their connection with mitochondrial impairment as well as oxidative stress and neuroinflammation.

中文翻译：

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脑铁蓄积（NBIA）引起的神经变性中的线粒体功能障碍，氧化应激和神经炎症

伴有脑铁积聚的神经退行性综合症（NBIA）涵盖了一组无效和进行性罕见疾病，它们与基底神经节中铁的异常积聚共享。NBIA疾病的发作期从婴儿期到成年期不等。主要的临床体征与锥体束外特征（肌张力障碍，帕金森氏症和胆脂症）以及神经精神异常有关。十种NBIA形式被广泛接受是由PANK2，PLA2G6，WDR45，C19ORF12，FA2H，ATP13A2，COASY，FTL1，CP和DCAF17基因突变引起的。尽管如此，许多患者仍未获得结论性的基因诊断，这表明必须存在其他尚未发现的NBIA基因。与此相符，已经描述了已知的单基因疾病的分离病例，以及新的遗传疾病，其表现出与NBIA相容的异常脑铁表型。NBIA综合征涉及几种途径：铁和脂质代谢，线粒体动力学和自噬。然而，鉴于神经元的生物能需求，许多神经退行性疾病具有共同的特征，例如线粒体功能障碍和氧化应激。这篇综述旨在通过检查经典的十种NBIA形式与线粒体损伤以及氧化应激和神经炎症的关系来描述它们之间的现有联系。