Tang Yi, Qin Qi, Xing Yi, Guo Dongmei, Di Li, Jia Jianping
Innovation Center for Neurological Disorders, Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Geriatric Cognitive Disorders, Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing, China.
Mol Genet Genomic Med. 2019 Apr;7(4):e00582. doi: 10.1002/mgg3.582. Epub 2019 Jan 31.
Mutations in the mitochondrial alanyl-transfer (t)RNA synthetase 2 (AARS2,OMIM:612035) have been linked to leukoencephalopathy recently. Till now, there have been 19 cases reported so far. However, the clinical and genetic characteristics of this disease are not fully understood. We reported an adult-onset male leukoencephalopathy patient related to novel AARS2 gene mutations and reviewed all previous cases regarding the clinical and genetic features of AARS2 leukoencephalopathy.
The spectrum of clinical symptoms and the genetic analysis of the presented patient were identified and investigated. Besides this case, we assessed previously reported cases with AARS2 gene mutations.
Here, we present a 30-year-old man with progressive motor deficits in the right lower limb and severe cerebellar ataxia for one year. MRI revealed extensive white matter lesions in periventricular regions and along the corticospinal tract. Genetic analysis revealed two new heterogeneous missense mutations in AARS2: c.179C>A and c.1703_1704del. We described the ragged red fiber (RRF) for the first time, suggesting that AARS2-related leukoencephalopathy be a new variant of mitochondrial encephalomyopathy. Gradual improvement in motor function was observed with intravenous coenzyme complex treatment. We also summarized our case and all previously reported cases to provide an overview of AARS2-related late-onset leukoencephalopathy. Then, we compared clinical and neuroimaging features of AARS2-related leukoencephalopathy with three other frequently diagnosed types of adult-onset leukoencephalopathy to provide insight into diagnostic strategies.
The characteristic MRI abnormalities and clinical symptoms described here may help to distinguish AARS2-related leukoencephalopathy from other adult-onset leukoencephalopathies. The combination of encephalopathy and myopathy strongly suggest that AARS2-related leukoencephalopathy is a new variant of mitochondrial encephalomyopathy. The response to coenzyme complex will shed light on future therapy investigation.
线粒体丙氨酰 - 转移（t）RNA合成酶2（AARS2，OMIM：612035）突变最近已被证实与白质脑病有关。到目前为止，已报道19例。然而，该疾病的临床和遗传特征尚未完全明确。我们报告了1例与新型AARS2基因突变相关的成年男性白质脑病患者，并回顾了之前所有关于AARS2白质脑病临床和遗传特征的病例。
对该患者的临床症状谱和基因分析进行鉴定和研究。除该病例外，我们评估了先前报道的携带AARS2基因突变的病例。
本文报告1例30岁男性，右下肢进行性运动功能障碍和严重小脑共济失调1年。磁共振成像（MRI）显示脑室周围区域和沿皮质脊髓束有广泛的白质病变。基因分析显示AARS2基因有两个新的异质性错义突变：c.179C>A和c.1703_1704del。我们首次描述了破碎红纤维（RRF），提示AARS2相关白质脑病是线粒体脑肌病的一种新变异型。静脉注射辅酶复合物治疗后观察到运动功能逐渐改善。我们还总结了本病例及所有先前报道的病例，以概述AARS2相关迟发性白质脑病。然后，我们将AARS2相关白质脑病的临床和神经影像学特征与其他三种常见的成年起病白质脑病类型进行比较，以深入了解诊断策略。
本文描述的特征性MRI异常和临床症状可能有助于将AARS2相关白质脑病与其他成年起病白质脑病区分开来。脑病和肌病的结合强烈提示AARS2相关白质脑病是线粒体脑肌病的一种新变异型。对辅酶复合物的反应将为未来的治疗研究提供线索。
