Okubo So, Matsukawa Takashi, Kawamoto Norifumi, Tsujita Masahiko, Orimo Kenta, Naruse Hiroya, Mitsui Jun, Hamada Masashi, Satake Wataru, Toda Tatsushi
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
J Hum Genet. 2025 Jul;70(7):381-384. doi: 10.1038/s10038-025-01342-0. Epub 2025 Apr 22.
PLA2G6-associated neurodegeneration (PLAN) encompasses a spectrum of phenotypes caused by biallelic pathogenic variants in PLA2G6. Initially linked to infantile and atypical neuroaxonal dystrophy, PLAN now includes adult-onset conditions such as dystonia-parkinsonism, ataxia, and spastic paraplegia. We report a female patient presenting young-onset parkinsonism with pyramidal tract signs, cerebellar atrophy, and autonomic dysfunction, mimicking multiple system atrophy (MSA). Neuroimaging showed decreased dopamine uptake and cerebellar hypoperfusion. Genetic analysis identified a homozygous pathogenic variant in PLA2G6 (c.967G>A, p.Val323Met), confirming a diagnosis of PLAN. Interestingly, elevated serum autotaxin levels (4.67 ng/mL) without liver abnormalities. Bilateral brachymetatarsia was also observed, which may indicate an association with the PLA2G6 variant. This case underscores the importance of considering PLAN in cases of young-onset parkinsonism with multisystem involvement. Genetic testing is crucial for accurate diagnosis and management of such cases. Elevated serum autotaxin levels may be associated with decreased phospholipase activity in PLAN and warrants further investigation.
磷脂酶A2G6相关神经变性(PLAN)涵盖了由PLA2G6双等位基因致病性变异引起的一系列表型。PLAN最初与婴儿型和非典型神经轴索性营养不良有关,现在包括成人发病的疾病,如肌张力障碍-帕金森综合征、共济失调和痉挛性截瘫。我们报告了一名女性患者,表现为早发性帕金森综合征,伴有锥体束征、小脑萎缩和自主神经功能障碍,酷似多系统萎缩(MSA)。神经影像学显示多巴胺摄取减少和小脑灌注不足。基因分析在PLA2G6中鉴定出一个纯合致病性变异(c.967G>A,p.Val323Met),确诊为PLAN。有趣的是,血清自分泌运动因子水平升高(4.67 ng/mL),且无肝脏异常。还观察到双侧短跖骨,这可能表明与PLA2G6变异有关。该病例强调了在早发性帕金森综合征伴多系统受累的病例中考虑PLAN的重要性。基因检测对于此类病例的准确诊断和管理至关重要。血清自分泌运动因子水平升高可能与PLAN中磷脂酶活性降低有关,值得进一步研究。