线粒体谷氨酰tRNA合成酶缺乏症,源于EARS2基因的双等位基因突变,于2012年首次描述。全球报告的病例少于50例,这种情况表现出新生儿或儿童期发病的独特表型,通常被称为丘脑和脑干受累和高乳酸(LTBL)的白质脑病。它也是所描述的少数可逆性线粒体疾病之一。这些患者的自然史记录很少,从临床和放射学改善到早期死亡。在这里,我们从中心详细介绍了三个案例,包括Steenweg等人报告的葡萄牙患者的随访。,这些病例说明了表型谱:i)乳酸血症和call体发育不全的快速进行性新生儿表现,导致早期死亡;ii)早期发作,缓慢进展过程;iii)早期发作,表型较温和,表现出一些改善和轻微的神经症状。此外,我们对EARS2缺陷患者的病例进行了系统的文献综述,注重临床表现,实验室发现,放射学方面,随着时间的推移和疾病的进展,以及各自的数据分析。“EARS2缺乏症患者通常在生命的第一年内出现明确的神经代谢紊乱情况,通常包括张力减退和/或痉挛,伴随神经发育迟缓或退化。没有特定于EARS2缺陷的病理特征,并且尚未发现基因型-表型相关性。“与Steenweg等人的初始表征相比。,这一分析揭示了扩大的疾病谱。我们提出了一种新的策略,将表型聚类为严重的,中度,或基于初始表现的轻度疾病,似乎与疾病进展有关。关于这种疾病的自然史的数据很少,这凸显了多中心方法来加强理解和管理的必要性。带回家的消息:对发表的所有EARS2缺乏症病例的分析可以建立疾病谱和与疾病进展相关的表型聚类的新策略。
Mitochondrial glutamyl-aminoacyl tRNA synthetase deficiency, stemming from biallelic mutations in the EARS2 gene, was first described in 2012. With <50 cases reported globally, this condition exhibits a distinct phenotype of neonatal or childhood-onset, often referred to as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). It has also been one of the few reversible
mitochondrial disorders described. The natural history of these patients is poorly documented, ranging from clinical and radiological improvement to early death. Herein, we detail three cases from our centre, including follow-up on the Portuguese patient reported by Steenweg et al., These cases illustrate the phenotypic spectrum: i) rapidly progressive neonatal presentation with lactic acidemia and corpus callosum agenesis, leading to early death; ii) early onset with a severe, slowly progressive course; iii) early onset with a milder phenotype, showing some improvement and mild neurological symptoms. Additionally, we conducted a systematic literature
review on cases of EARS2-deficient patients, focusing on clinical manifestations, laboratory findings, radiological aspects, and disease progression over time, along with respective data analysis. \"Patients with EARS2 deficiency typically present within the first year of life with a well-defined neurometabolic disorder picture, often including hypotonia and/or spasticity, along with neurodevelopmental delay or regression. There are no pathognomonic features specific to EARS2 deficiency, and no genotype-phenotype correlation has been identified.\" Comparing to initial characterization by Steenweg et al., this analysis reveals an expanded disease spectrum. We propose a novel strategy for clustering phenotypes into severe, moderate, or mild disease based on initial presentation, seemingly correlating with disease progression. The paucity of data on the disease\'s natural history highlights the need for a multicentric approach to enhance understanding and management. TAKE-HOME MESSAGE: Analysis of all cases published with EARS2 deficiency allows for establish disease spectrum and a novel strategy for clustering phenotypes which correlate to disease progression.