Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland.
Parkinsonism Relat Disord. 2022 Aug;101:66-74. doi: 10.1016/j.parkreldis.2022.06.016. Epub 2022 Jun 30.
PLA2G6-Associated Neurodegeneration, PLAN, is subdivided into: Infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, and adult-onset dystonia parkinsonism [1]. It is elicited by a biallelic pathogenic variant in phospholipase A2 group VI (PLA2G6) gene. In this study we describe new cases and provide a comprehensive review of previously published cases.
Eleven patients, from four different institutions and four different countries. All underwent a comprehensive chart review.
Ages at onset ranged from 1 to 36 years, with a median of 16 and a mean of 16.18 ± 11.91 years. Phenotypic characteristics were heterogenous and resembled that of patients with infantile neuroaxonal dystrophy (n = 2), atypical neuroaxonal dystrophy (n = 1), adult-onset dystonia parkinsonism (n = 1), complex hereditary spastic paraparesis (n = 3), and early onset Parkinson's disease (n = 2). Parental genetic studies were performed for all patients and confirmed with sanger sequencing in five. Visual evoked potential illustrated optic atrophy in P4. Mineralization was evident in brain magnetic resonance imaging of P1, P2, P4, P5, P7, and P11. Single photon emission computed tomography was conducted for three patients, revealed decreased perfusion in the occipital lobes for P10. DaTscan was performed for P11 and showed decreased uptake in the deep gray matter, bilateral caudate nuclei, and bilateral putamen. Positive response to Apomorphine was noted for P10 and to Baclofen in P2, and P3.
PLAN encompasses a wide clinical spectrum. Age and symptom at onset are crucial when classifying patients. Reporting new variants is critical to draw more attention to this condition and identify biomarkers to arrive at potential therapeutics.
PLA2G6 相关神经退行性疾病，PLAN，分为：婴儿型神经轴索性营养不良、非典型神经轴索性营养不良和成人发作性肌张力障碍帕金森病[1]。它由磷脂酶 A2 组 VI (PLA2G6) 基因的双等位致病性变异引起。在这项研究中，我们描述了新病例，并对以前发表的病例进行了全面回顾。
来自四个不同机构和四个不同国家的 11 名患者。所有患者均接受了全面的病历回顾。
发病年龄从 1 岁到 36 岁不等，中位数为 16 岁，平均年龄为 16.18±11.91 岁。表型特征各不相同，类似于婴儿型神经轴索性营养不良（n=2）、非典型神经轴索性营养不良（n=1）、成人发作性肌张力障碍帕金森病（n=1）、复杂遗传性痉挛性截瘫（n=3）和早发性帕金森病（n=2）患者。对所有患者进行了父母遗传研究，并在 5 例中通过 Sanger 测序进行了确认。视觉诱发电位显示 P4 有视神经萎缩。P1、P2、P4、P5、P7 和 P11 的脑磁共振成像显示有矿化。对 3 名患者进行了单光子发射计算机断层扫描，显示 P10 枕叶灌注减少。对 P11 进行了 DaTscan，显示深部灰质、双侧尾状核和双侧壳核摄取减少。P10 对阿扑吗啡有阳性反应，P2 和 P3 对巴氯芬有阳性反应。
PLAN 涵盖了广泛的临床谱。年龄和发病时的症状对于分类患者至关重要。报告新的变异对于引起对这种情况的更多关注并识别生物标志物以实现潜在的治疗方法非常重要。
