Biostatistics and Bioinformatics Program, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
Division of Pediatric Genetics, Department of Pediatrics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
BMC Med Genomics. 2021 Jul 31;14(1):197. doi: 10.1186/s12920-021-01045-3.
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.
GLUT1 缺乏症 1 型（GLUT1DS1）是一种由溶质载体家族 2，成员 1（SLC2A1）基因突变引起的神经系统疾病，可为杂合子或纯合子突变。SLC2A1 基因编码葡萄糖转运蛋白 1（GLUT1）蛋白，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，我们在一名患有癫痫的女孩中发现了一种新的杂合 SLC2A1 变体。在通过神经代谢测试反向表型后，她被诊断为 GLUT1DS1 并开始接受 KD 治疗。患者的症状对饮食有反应。在这里，我们报告了一名患有 GLUT1DS1 的患者，该患者存在一种新的 SLC2A1 突变。她还有一个此前未与该综合征相关的血管瘤。
一名 5 岁 8 个月大的女孩，表现为全面发育迟缓、痉挛、智力障碍、构音障碍性言语、眼球运动异常和血管瘤。脑电图（EEG）结果显示她患有癫痫。磁共振成像（MRI）显示非特异性白质异常。全外显子组测序（WES）之前已经进行，但病例仍未解决。对 WES 数据的重新分析显示 SLC2A1 基因的剪接变异杂合子。用父母 DNA 样本进行的分离分析表明，该变体是新生的。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。自开始饮食以来，她很快就没有了癫痫发作。饮食后，她的不自主运动减少，言语变得更容易理解，词汇量增加。
我们在一名之前 WES 结果为阴性的患者的 SLC2A1 基因中发现了一种新的新生变异。该患者被诊断为 GLUT1DS1。该综合征是一种可治疗的疾病，但由于表现出广泛的表型谱和与其他神经疾病重叠的症状，其鉴别诊断并不是一个简单的过程。诊断需要进行基因组检测。我们的发现还强调了对初始 WES 后未确诊病例进行重新分析以揭示致病变异的重要性。
