Movement Disorders Unit, Neurology Department, Westmead Hospital, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
Movement Disorders Unit, Neurology Department, Westmead Hospital, NSW, Australia.
Parkinsonism Relat Disord. 2019 Jul;64:319-323. doi: 10.1016/j.parkreldis.2019.04.004. Epub 2019 Apr 5.
Phosphoglycerate kinase-1 deficiency is caused by X-linked recessive mutations in PGK-1 and associated with haemolytic anaemia, rhabdomyolysis, myopathy and nervous system involvement. Some cases have been rarely associated with juvenile Parkinsonism however the causal relationship between PGK1 deficiency and nigrostriatal dysfunction causing Parkinsonism has not been determined.
To investigate the nigrostriatal system using 99mTc-TRODAT-1 SPECT binding and report the phenotype of three affected males with early onset levodopa responsive Parkinsonism harbouring the c.491 A > T/p.D164V pathogenic variant.
All patients initially presented with infantile-onset encephalopathic and stroke-like episodes, haemolytic anaemia and epilepsy. Two patients had an early-onset and one juvenile-onset levodopa responsive Parkinsonism with motor fluctuations. 99mTc-TRODAT-1 SPECT showed severe bilateral reduced putaminal uptake in the three patients. None of the patients had structural lesions that could explain either pre- or postsynaptic dopaminergic dysfunction.
These cases provide strong evidence of a causal relationship between PGK1 deficiency and nigrostriatal pathology causing Parkinsonism. These findings have potential implications for our understanding of the pathophysiology of nigrostriatal degeneration in sporadic PD.
磷酸甘油激酶-1 缺乏症是由 PGK-1 的 X 连锁隐性突变引起的，与溶血性贫血、横纹肌溶解症、肌病和神经系统受累有关。一些病例罕见地与青少年帕金森病有关，但 PGK1 缺乏症与导致帕金森病的黑质纹状体功能障碍之间的因果关系尚未确定。
使用 99mTc-TRODAT-1 SPECT 结合来研究黑质纹状体系统，并报告携带 c.491 A>T/p.D164V 致病性变异的 3 名早发性左旋多巴反应性帕金森病男性患者的表型。
所有患者最初表现为婴儿期脑病和类似中风发作、溶血性贫血和癫痫。2 名患者有早发性和 1 名青少年起病的左旋多巴反应性帕金森病，伴有运动波动。99mTc-TRODAT-1 SPECT 显示 3 名患者双侧纹状体摄取严重减少。患者均无结构病变，无法解释其突触前或突触后多巴胺能功能障碍。
这些病例为 PGK1 缺乏症与导致帕金森病的黑质纹状体病理之间的因果关系提供了有力证据。这些发现可能对我们理解散发性帕金森病黑质纹状体变性的病理生理学具有潜在意义。
