So Okubo, Takashi Matsukawa, Norifumi Kawamoto, Masahiko Tsujita, Kenta Orimo, Hiroya Naruse, Jun Mitsui, Masashi Hamada, Wataru Satake, Tatsushi Toda
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引用次数: 0
摘要
PLA2G6相关神经变性(PLAN)包括PLA2G6双等位基因致病变异引起的表型谱。PLAN最初与婴儿和非典型神经轴突营养不良有关,现在包括成人发病的疾病,如肌张力障碍-帕金森病、共济失调和痉挛性截瘫。我们报告一位年轻发病的女性帕金森患者,伴有锥体束体征,小脑萎缩和自主神经功能障碍,模拟多系统萎缩(MSA)。神经影像学显示多巴胺摄取减少,小脑灌注不足。遗传分析在PLA2G6中发现纯合致病变异(c.967G> a, p.Val323Met),证实了PLAN的诊断。有趣的是,血清autotaxin水平升高(4.67 ng/mL),无肝脏异常。还观察到双侧近视,这可能表明与PLA2G6变异有关。本病例强调了在多系统累及的年轻起病帕金森病例中考虑计划治疗的重要性。基因检测对于这些病例的准确诊断和管理至关重要。血清自体的士素水平升高可能与PLAN中磷脂酶活性降低有关,值得进一步研究。
Elevated serum autotaxin levels and multiple system atrophy-like presentation in a patient with PLA2G6-associated neurodegeneration.
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.
期刊介绍:
The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy.
Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.