The First Metabolome Analysis in Children with Epilepsy and ALG13-CDG Resulting from c.320A>G Variant

被引:5
作者
Paprocka, Justyna [1 ]
Jezela-Stanek, Aleksandra [2 ]
Boguszewicz, Lukasz [3 ]
Sokol, Maria [3 ]
Lipinski, Patryk [4 ]
Jamroz, Ewa [1 ]
Emich-Widera, Ewa [1 ]
Tylki-Szymanska, Anna [4 ]
机构
[1] Med Univ Silesia, Dept Pediat Neurol, Fac Med Sci Katowice, PL-40055 Katowice, Poland
[2] Natl Inst TB & Lung Dis, Dept Genet & Clin Immunol, PL-01138 Warsaw, Poland
[3] Maria Sklodowska Curie Natl Res Inst Oncol, Dept Med Phys, PL-44102 Gliwice, Poland
[4] Childrens Mem Hlth Inst, Dept Pediat Nutr & Metab Disorders, PL-04730 Warsaw, Poland
来源
CHILDREN-BASEL | 2021年 / 8卷 / 03期
关键词
ALG13-CDG; c.320A > G variant (p.Asn107Ser); epilepsy; metabolome; CONGENITAL DISORDERS; INBORN-ERRORS; GLYCOSYLATION; CARNITINE; BETAINE;
D O I
10.3390/children8030251
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Background: 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 ALG13, 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. Methods: 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. Results: Three metabolites were identified as potential biomarkers: betaine, N-acetyl-glycoprotein, and carnitine. Conclusions: 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.
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页数:13
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