GLUT1 Deficiency Syndrome 1 (GLUT1DS1) is a neurological disorder caused by either heterozygous or homozygous mutations in the Solute Carrier Family 2, Member 1 (SLC2A1) gene. SLC2A1 encodes Glucose transporter type 1 (GLUT1) protein, which is the primary glucose transporter at the blood–brain barrier. A ketogenic diet (KD) provides an alternative fuel for brain metabolism to treat impaired glucose transport. By reanalyzing exome data, we identified a de novo heterozygous SLC2A1 variant in a girl with epilepsy. After reversed phenotyping with neurometabolic tests, she was diagnosed with GLUT1DS1 and started on a KD. The patient's symptoms responded to the diet. Here, we report a patient with GLUT1DS1 with a novel SLC2A1 mutation. She also has a hemangioma which has not been reported in association with this syndrome before. A 5-year 8-month girl with global developmental delay, spasticity, intellectual disability, dysarthric speech, abnormal eye movements, and hemangioma. The electroencephalography (EEG) result revealed that she had epilepsy. Magnetic resonance imaging (MRI) showed that non-specific white matter abnormalities. Whole Exome Sequencing (WES) was previously performed, but the case remained unsolved. The re-analysis of WES data revealed a heterozygous splicing variant in the SLC2A1 gene. Segregation analysis with parental DNA samples indicated that the variant occurred de novo. Lumbar puncture (LP) confirmed the diagnosis, and the patient started on a KD. Her seizures responded to the KD. She has been seizure-free since shortly after the initiation of the diet. She also had decreased involuntary movements, her speech became more understandable, and her vocabulary increased after the diet. We identified a novel de novo variant in the SLC2A1 gene in a patient who previously had a negative WES result. The patient has been diagnosed with GLUT1DS1. The syndrome is a treatable condition, but the differential diagnosis is not an easy process due to showing a wide range of phenotypic spectrum and the overlapping symptoms with other neurological diseases. The diagnosis necessitates a genomic testing approach. Our findings also highlight the importance of re-analysis to undiagnosed cases after initial WES to reveal disease-causing variants.

中文翻译：

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全外显子组测序数据的重新分析揭示了伴有血管瘤的 GLUT1 缺乏综合征 1 患者 SLC2A1 中的一种新剪接变异：病例报告


GLUT1 缺乏综合症 1 (GLUT1DS1) 是一种由溶质载体家族 2 成员 1 (SLC2A1) 基因杂合或纯合突变引起的神经系统疾病。 SLC2A1 编码 1 型葡萄糖转运蛋白 (GLUT1) 蛋白，它是血脑屏障的主要葡萄糖转运蛋白。生酮饮食（KD）为大脑代谢提供替代燃料，以治疗葡萄糖转运受损。通过重新分析外显子组数据，我们在一名癫痫女孩身上发现了一个从头杂合的 SLC2A1 变异。通过神经代谢测试进行逆转表型分析后，她被诊断患有 GLUT1DS1 并开始服用 KD。患者的症状对饮食有反应。在此，我们报告了一名患有 GLUT1DS1 且具有新型 SLC2A1 突变的患者。她还患有血管瘤，此前尚未有与该综合征相关的报道。一名 5 岁 8 个月的女孩，患有全身性发育迟缓、痉挛、智力障碍、构音障碍、眼球运动异常和血管瘤。脑电图（EEG）结果显示她患有癫痫症。磁共振成像（MRI）显示白质非特异性异常。此前曾进行过全外显子组测序（WES），但此案仍未解决。 WES 数据的重新分析揭示了 SLC2A1 基因中的杂合剪接变异。对亲本 DNA 样本的分离分析表明，该变异是从头发生的。腰椎穿刺 (LP) 证实了诊断，患者开始接受 KD 治疗。她的癫痫发作对 KD 有反应。自从开始节食后不久，她就没有再癫痫发作。节食后，她的不自主运动也减少了，她的言语变得更容易理解，词汇量也增加了。 我们在一名先前 WES 结果呈阴性的患者身上发现了 SLC2A1 基因中的一种新的从头变异。该患者已被诊断患有 GLUT1DS1。该综合征是一种可以治疗的疾病，但由于表现出广泛的表型谱以及与其他神经系统疾病的重叠症状，鉴别诊断并不是一个容易的过程。诊断需要基因组测试方法。我们的研究结果还强调了在初次 WES 后对未确诊病例进行重新分析以揭示致病变异的重要性。