Neurology Clinic, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Institute for Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Neurol India. 2021 Sep-Oct;69(5):1380-1388. doi: 10.4103/0028-3886.329603.
A disturbed iron metabolism may damage brain and trigger disorders known as neurodegeneration with brain iron accumulation (NBIA). NBIAs are rare, inherited disorders in which responsible mutations affect the function of proteins that participate in tissue iron homeostasis. Accumulated iron, which may be recognized as a low signal intensity on T2-weighted MRI images, oftentimes points to a diagnosis. Recent genetic discoveries confirm that NBIA is not a homogenous group of diseases. Fifteen different NBIAs have been described to date; among these, autosomal recessive inheritance was reported in 13, and autosmal dominant and X-linked dominant inheritance in one disease, respectively. Among NBIAs, the most common is pantothenate kinase-associated neurodegeneration (PKAN-NBIA 1) (30%-50% of all NBIA cases), that occurrs as a consequence of the autosomal recessive mutation in PANK2 gene, followed by phospholipase 2-associated neurodegeneration (PLAN, NBIA 2), due to mutation in PLA2G6 gene, and mitochondrial membrane protein-associated neurodegeneration (MPAN) with the underlying C19orf12 mutation [Table 1]. NBIAs are characterized by complex motor presentations from early-onset degeneration and premature fatality to adult-onset parkinsonism and dystonia. Epileptic seizures, pyramidal signs, visual disorders, and cognitive deterioration can develop. NBIAs are often refractory to therapeutical strategies, although certain interventions may provide significant symptomatic relief in selected patients. In this review, we discuss the expanding clinical spectrum of these complex and rare syndromes, their genetic and imaging features, and potential therapeutical targets and strategies.
铁代谢紊乱可能会损害大脑并引发神经退行性疾病，称为脑铁蓄积的神经退行性疾病（NBIA）。NBIA 是罕见的遗传性疾病，其相关突变会影响参与组织铁稳态的蛋白质的功能。在 T2 加权 MRI 图像上，铁的积累通常表现为低信号强度，这常常指向诊断。最近的遗传发现证实，NBIA 不是一组同质的疾病。迄今为止，已经描述了 15 种不同的 NBIA；其中，13 种为常染色体隐性遗传，1 种为常染色体显性遗传和 X 连锁显性遗传。在 NBIA 中，最常见的是泛酸激酶相关神经退行性变（PKAN-NBIA 1）（所有 NBIA 病例的 30%-50%），这是由于 PANK2 基因突变引起的常染色体隐性遗传，其次是磷脂酶 2 相关神经退行性变（PLAN，NBIA 2），这是由于 PLA2G6 基因突变引起的，以及线粒体膜蛋白相关神经退行性变（MPAN），其潜在的 C19orf12 突变[表 1]。NBIA 的特点是复杂的运动表现，从早发性退行性变和早发性死亡到成年期帕金森病和肌张力障碍。可能会出现癫痫发作、锥体束征、视力障碍和认知功能恶化。NBIA 通常对治疗策略有抗性，尽管某些干预措施可能会为某些患者提供显著的症状缓解。在这篇综述中，我们讨论了这些复杂且罕见的综合征不断扩大的临床谱，以及它们的遗传和成像特征以及潜在的治疗靶点和策略。
