Biallelic variants in the NARS2 gene are the cause of a continuous spectrum of neurodegenerative disorders presenting with various severity-from spastic paraplegia, progressive neurodegeneration to Leigh and Alpers syndrome. Common clinical signs result from a mitochondrial dysfunction based on OXPHOS deficiency. Here, we present a patient with infantile-onset severe epilepsy leading to fatal refractory status epilepticus. Whole exome sequencing with Exomiser analysis based on HPO terms detected two novel NARS2 variants in a compound heterozygous state. To date, 18 different NARS2 disease-causing mutations have been described. Our study adds to the understanding of this mitochondrial disorder.

NARS2 基因中的双等位基因变异是一系列神经退行性疾病的原因，这些疾病表现出不同的严重程度——从痉挛性截瘫、进行性神经退行性变到 Leigh 和 Alpers 综合征。常见的临床症状是由基于 OXPHOS 缺乏的线粒体功能障碍引起的。在这里，我们介绍了一名婴儿期严重癫痫患者，导致致命的难治性癫痫持续状态。基于 HPO 术语的 Exomiser 分析的全外显子组测序检测到两种处于复合杂合状态的新型NARS2变体。迄今为止，已经描述了18 种不同的NARS2致病突变。我们的研究增加了对这种线粒体疾病的理解。