Gordon Neil
Huntlywood, 3 Styal Road, Wilmslow, Cheshire SK9 4AE, UK.
Eur J Paediatr Neurol. 2002;6(5):243-7. doi: 10.1053/ejpn.2002.0606.
The arguments over the nomenclature of the syndrome are reviewed. Ethical considerations favour replacing the present eponyms with the title of panthothenate kinase-associated neurodegeneration (PKAN), now that more is known about the cause of the condition. The symptoms and signs of the syndrome are described, and these can present from infancy to adult life. Dystonia, involuntary movements and spasticity are prominent causes of disability. If the onset is delayed the presentation can be unusual. Tests that can help in diagnosis are reviewed, especially the "eye of the tiger" revealed by magnetic resonance imaging scanning. Death usually occurs about 10 years after the onset, but the course may be more prolonged. The findings on autopsy are also considered, with the typical findings of iron pigment deposits and axonal spheroids. Then the causes are discussed. Once the responsible gene PANK2 had been discovered on chromosome 20 it was found that this encoded for pantothenate kinase which is essential for the synthesis of coenzyme A from pantothenate; and this is integral to fatty acid synthesis and energy metabolism. Also this can lead to a concentration of cysteine in the basal ganglia, and then to an accumulation of iron in these areas. The cysteine-iron complex will result in tissue damage by promoting oxidative stress, as in some other neurodegenerative diseases. The syndrome of PKAN can therefore be identified as a disorder of pantothanate, vitamin B5, metabolism. Infantile neuroaxonal dystrophy is briefly described as there have been suggestions that it is a variety of PKAN, but the evidence is in favour of the two diseases being separate entities. There may as yet be no specific treatment for this syndrome, but much can be done to help these children. Drugs may be needed to control epilepsy, and when dystonia is severe it may be possible to alleviate this by medical or surgical means. Also there will be other problems needing expert management, such as the provision of alternative means of communication if dysarthria is marked. The hope for the future is that now the cause has been found it will be possible to use methods such as antioxidative therapy and gene induction procedures.
本文回顾了关于该综合征命名的争论。鉴于目前对该病症病因有了更多了解，从伦理角度考虑，倾向于用泛酸激酶相关神经变性（PKAN）这一名称取代现有的以人名命名的称谓。文中描述了该综合征的症状和体征，其可在婴儿期至成年期出现。肌张力障碍、不自主运动和痉挛是导致残疾的主要原因。如果发病延迟，其表现可能不寻常。文中回顾了有助于诊断的检查，尤其是磁共振成像扫描显示的“虎眼征”。死亡通常在发病后约10年发生，但病程可能更长。文中还考虑了尸检结果，其典型表现为铁色素沉积和轴突球体。接着讨论了病因。一旦在20号染色体上发现了致病基因PANK2，就发现它编码泛酸激酶，而泛酸激酶对于从泛酸合成辅酶A至关重要；这对于脂肪酸合成和能量代谢不可或缺。此外，这会导致基底节中半胱氨酸浓度升高，进而导致这些区域铁的蓄积。半胱氨酸 - 铁复合物会像其他一些神经退行性疾病一样，通过促进氧化应激导致组织损伤。因此，PKAN综合征可被确定为一种泛酸（维生素B5）代谢紊乱疾病。简要描述了婴儿型神经轴索性营养不良，因为有人认为它是PKAN的一种类型，但现有证据支持这两种疾病是独立的实体。该综合征目前可能尚无特效治疗方法，但可以做很多事情来帮助这些患儿。可能需要药物来控制癫痫，当肌张力障碍严重时，或许可以通过药物或手术手段缓解。此外，还会有其他问题需要专家处理，比如如果构音障碍明显，需提供替代沟通方式。未来的希望是，既然已经找到了病因，或许可以采用抗氧化治疗和基因诱导程序等方法。
