Abstract
BackgroundGLUT1 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.Case presentationA 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.ConclusionsWe 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.
Highlights
Glucose transporter type 1 (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
We identified a novel de novo variant in the SLC2A1 gene in a patient who previously had a negative Whole Exome Sequencing (WES) result
The patient has been diagnosed with GLUT1DS1
Summary
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. The Solute Carrier Family 2, Member 1 gene (SLC2A1, OMIM *138140) is located on the 1p34.2 and encodes Glucose transporter type 1 (GLUT1) composed of 492 amino acids [1, 2]. Impaired glucose transport at the blood–brain barrier caused by mutations in the SLC2A1 result in GLUT1 Deficiency Syndrome 1 (GLUT1DS1, OMIM #606777), which is a rare neurometabolic disorder [6, 7]. The CSF/blood glucose ratio is usually less than 0.4 and CSF glucose level should be less than 60 mg/dl for the diagnosis [10] Another sign for the syndrome is the SLC2A1 mutations which predominantly occur de novo with the autosomal dominant condition [11]. It is vital to identify GLUT1DS1 in the early stages since the ketogenic diet (KD) therapy has the potential to improve symptoms [20]
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