Gautam Mukesh, Carratore Renata Del, Helmold Benjamin, Tessa Alessandra, Gozutok Oge, Chandel Navdeep, Idrisoglu Halil, Bongioanni Paolo, Battini Roberta, Ozdinler P Hande
Department of Neurology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL 60611, USA.
Clinical Physiology Institute of National Council of Research, Via Moruzzi 1, 56100 Pisa, Italy.
Metabolites. 2022 Feb 12;12(2):174. doi: 10.3390/metabo12020174.
Pathogenic variants in have been detected mostly in juvenile cases of amyotrophic lateral sclerosis (ALS), affecting mainly children and teenagers. Patients with mutations demonstrate early onset cortical involvement in ALS. Currently, there are no effective treatment options. There is an immense need to reveal the underlying causes of the disease and to identify potential biomarkers. To shed light onto the metabolomic events that are perturbed with respect to mutations, we investigated the metabolites present in the serum and plasma of a three-year-old female patient (AO) harboring pathogenic variants in , together with her relatives, healthy male and female controls, as well as another two-year-old patient DH, who had mutations at different locations and domains of . Serum and plasma samples were analyzed with a quantitative metabolomic approach to reveal the identity of metabolites present in serum and plasma. This study not only shed light onto the perturbed cellular pathways, but also began to reveal the presence of a distinct set of key metabolites that are selectively present or absent with respect to mutations, laying the foundation for utilizing metabolites as potential biomarkers for a subset of ALS.
已在肌萎缩侧索硬化症（ALS）的青少年病例中大多检测到[具体基因名称]的致病变体，主要影响儿童和青少年。携带[具体基因名称]突变的患者在ALS中表现出早期皮质受累。目前，尚无有效的治疗选择。迫切需要揭示该疾病的潜在病因并确定潜在的生物标志物。为了阐明与[具体基因名称]突变相关的代谢组学事件，我们研究了一名携带[具体基因名称]致病变体的三岁女性患者（AO）及其亲属、健康男性和女性对照以及另一名两岁患者DH（其[具体基因名称]在不同位置和结构域发生突变）的血清和血浆中的代谢物。采用定量代谢组学方法分析血清和血浆样本，以揭示血清和血浆中存在的代谢物的身份。这项研究不仅阐明了受干扰的细胞途径，还开始揭示存在一组独特的关键代谢物，它们相对于[具体基因名称]突变有选择性地存在或不存在，为将代谢物用作一部分ALS的潜在生物标志物奠定了基础。
