Department of Developmental Neurology, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznan, Poland.
Institute of Mother and Child, Department of Medical Genetics, ul. Kasprzaka 17A, 01-211 Warsaw, Poland.
Epilepsy Behav. 2020 May;106:107036. doi: 10.1016/j.yebeh.2020.107036. Epub 2020 Apr 1.
Glucose transporter type 1 deficiency (G1D) syndrome is generally a genetic disorder because of a mutation of the SLC2A1 gene. The clinical picture of G1D is heterogeneous. The aim of this paper was to present the case of G1D, recognized in a three-generation family, caused by missense mutation p.Arg92Trp in SLC2A1 gene, and showing high clinical heterogeneity and evolution of symptoms over time.
Three-generation family members, showing symptoms suggesting G1D, have been characterized in terms of the clinical picture, electroencephalogram (EEG) recordings, brain neuroimaging, and the psychological assessment data. All subjects were offered genetic testing of the SLC2A1 gene.
We sequenced the SLC2A1 gene in the proband of the family and identified the c.274C > T variant (p.Arg92Trp). The presence of the same mutation was confirmed in all affected family members; however, significant variations in the clinical picture among them were observed. In addition to the typical symptoms for G1D (e.g., epilepsy, intellectual disability), patients presented movement disorders, stiffness, and dysarthria, as well as psychiatric symptoms. After using the ketogenic diet, epileptic seizures disappeared, but the rest of the symptoms were resistant to treatment.
Despite the same underlying mutation, clinical symptoms may vary among members of one family. Different clinical symptoms are observed depending on the patient's age. Not all symptoms occur in all patients within one family despite the same genetic background. However, the importance of early therapy for the clinical course of the disease requires further study.
葡萄糖转运蛋白 1 缺乏症（G1D）综合征通常是一种遗传疾病，由于 SLC2A1 基因突变所致。G1D 的临床表现具有异质性。本文旨在报告一个三代表现 G1D 的家系病例，该病例由 SLC2A1 基因的错义突变 p.Arg92Trp 引起，表现出较高的临床异质性和症状随时间的演变。
对具有 G1D 症状的三代家系成员进行临床表型、脑电图（EEG）记录、脑神经影像学和心理评估数据的特征描述。所有受试者均接受 SLC2A1 基因突变检测。
我们对家系中的先证者进行了 SLC2A1 基因测序，发现了 c.274C>T 变异（p.Arg92Trp）。该突变在所有受影响的家系成员中均存在，但他们的临床表现存在显著差异。除了 G1D 的典型症状（如癫痫、智力障碍）外，患者还表现出运动障碍、僵硬和构音障碍以及精神症状。在使用生酮饮食后，癫痫发作消失，但其余症状仍难以治疗。
尽管存在相同的潜在突变，但一个家系成员的临床表现可能存在差异。不同的临床症状随患者年龄而变化。尽管具有相同的遗传背景，但并非所有患者都会出现同一家庭内的所有症状。然而，早期治疗对疾病的临床病程至关重要，需要进一步研究。
