Paprocka Justyna, Jezela-Stanek Aleksandra, Boguszewicz Łukasz, Sokół Maria, Lipiński Patryk, Jamroz Ewa, Emich-Widera Ewa, Tylki-Szymańska Anna
Department of Pediatric Neurology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland.
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland.
Children (Basel). 2021 Mar 23;8(3):251. doi: 10.3390/children8030251.
ALG13-CDG belongs to the congenital disorders of glycosylation (CDG), which is an expanding group of multisystemic metabolic disorders caused by the N-linked, O-linked oligosaccharides, shared substrates, glycophosphatidylinositol (GPI) anchors, and dolichols pathways with high genetic heterogeneity. Thus, as far as clinical presentation, laboratory findings, and treatment are concerned, many questions are to be answered. Three individuals presented here may serve as a good example of clinical heterogeneity. This manuscript describes the first metabolomic analysis using NMR in three patients with epileptic encephalopathy due to the recurrent c.320A>G variant in characterized to date only in about 60 individuals (mostly female). This is an important preliminary step in the understanding of the pathogenesis of the disease associated with this variant in the rare genetic condition. The disease is assumed to be a disorder of N-glycosylation given that this is the only known function of the ALG13 protein. Despite this, protein electrophoresis, which is abnormal in most conditions due to abnormalities in N-glycosylation, has been normal or only mildly abnormal in the ALG13 patients.
Nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate and univariate modelling were used to analyze the metabolic profile of the blood serum samples acquired from the studied patients.
Three metabolites were identified as potential biomarkers: betaine, N-acetyl-glycoprotein, and carnitine.
Since presented data are the first to be collected so far, they need be verified in further studies. Our intention was to turn attention toward possible CDG-ALG13 laboratory markers that would have clinical significance.
ALG13 - CDG属于糖基化先天性疾病（CDG），这是一组不断扩大的多系统代谢紊乱疾病，由N - 连接、O - 连接寡糖、共享底物、糖基磷脂酰肌醇（GPI）锚定物和多萜醇途径引起，具有高度的遗传异质性。因此，就临床表现、实验室检查结果和治疗而言，有许多问题有待解答。这里介绍的三名患者可作为临床异质性的一个很好的例子。本手稿描述了首例使用核磁共振（NMR）对三名因复发性c.320A>G变异导致癫痫性脑病的患者进行代谢组学分析，该变异迄今为止仅在约60人（大多数为女性）中得到表征。这是了解这种罕见遗传疾病中与该变异相关疾病发病机制的重要初步步骤。鉴于这是已知的ALG13蛋白的唯一功能，该疾病被认为是一种N - 糖基化紊乱。尽管如此，在大多数因N - 糖基化异常而出现异常的情况下，蛋白电泳在ALG13患者中一直正常或仅轻度异常。
结合多变量和单变量建模的核磁共振（NMR）光谱用于分析从研究患者采集的血清样本的代谢谱。
三种代谢物被鉴定为潜在生物标志物：甜菜碱、N - 乙酰糖蛋白和肉碱。
由于目前呈现的数据是迄今为止首次收集的数据，需要在进一步研究中进行验证。我们的目的是将注意力转向可能具有临床意义的CDG - ALG13实验室标志物。
