GLUT1 Deficiency Syndrome-Early Treatment Maintains Cognitive Development? (Literature Review and Case Report)

doi:10.3390/genes12091379

Review

. 2021 Aug 31;12(9):1379.

doi: 10.3390/genes12091379.

GLUT1 Deficiency Syndrome-Early Treatment Maintains Cognitive Development? (Literature Review and Case Report)

Ivana Kolic^{1

2}, Jelena Radic Nisevic^{1

3}, Inge Vlasic Cicvaric^{3

4}, Ivona Butorac Ahel^{1

3}, Kristina Lah Tomulic^{1

3}, Silvije Segulja^{1

2}, Kristina Baraba Dekanic^{1

2}, Senada Serifi^{1

3}, Aleksandar Ovuka¹, Igor Prpic^{1

3}

Affiliations

¹ Pediatric Clinic, Clinical Hospital Center Rijeka, Kresimirova 42, 51000 Rijeka, Croatia.
² Department of Clinical Science, Faculty of Health Studies, University of Rijeka, Viktora Cara Emina 5, 51000 Rijeka, Croatia.
³ Department of Pediatrics, School of Medicine Rijeka, University of Rijeka, Brace Branchetta 20/1, 51000 Rijeka, Croatia.
⁴ Department of Clinical, Health and Organizational Psychology, Clinical Hospital Center Rijeka, Kresimirova 42, 51000 Rijeka, Croatia.

PMID: 34573360
PMCID: PMC8472230
DOI: 10.3390/genes12091379

Review

GLUT1 Deficiency Syndrome-Early Treatment Maintains Cognitive Development? (Literature Review and Case Report)

Ivana Kolic et al. Genes (Basel). 2021.

. 2021 Aug 31;12(9):1379.

doi: 10.3390/genes12091379.

Authors

Affiliations

¹ Pediatric Clinic, Clinical Hospital Center Rijeka, Kresimirova 42, 51000 Rijeka, Croatia.
² Department of Clinical Science, Faculty of Health Studies, University of Rijeka, Viktora Cara Emina 5, 51000 Rijeka, Croatia.
³ Department of Pediatrics, School of Medicine Rijeka, University of Rijeka, Brace Branchetta 20/1, 51000 Rijeka, Croatia.
⁴ Department of Clinical, Health and Organizational Psychology, Clinical Hospital Center Rijeka, Kresimirova 42, 51000 Rijeka, Croatia.

PMID: 34573360
PMCID: PMC8472230
DOI: 10.3390/genes12091379

Abstract

Glucose transporter type 1 (GLUT1) is the most important energy carrier of the brain across the blood-brain barrier, and a genetic defect of GLUT1 is known as GLUT1 deficiency syndrome (GLUT1DS). It is characterized by early infantile seizures, developmental delay, microcephaly, ataxia, and various paroxysmal neurological phenomena. In most cases, GLUT1DS is caused by heterozygous single-nucleotide variants (SNVs) in the SLC2A1 gene that provoke complete or severe impairment of the functionality and/or expression of GLUT1 in the brain. Despite the rarity of these diseases, GLUT1DS is of high clinical interest since a very effective therapy, the ketogenic diet, can improve or reverse symptoms, especially if it is started as early as possible. We present a clinical phenotype, biochemical analysis, electroencephalographic and neuropsychological features of an 11-month-old boy with myoclonic seizures, hypogammaglobulinemia, and mildly impaired gross motor development. Using sequence analysis and deletion/duplication testing, deletion of an entire coding sequence in the SLC2A1 gene was detected. Early introduction of a modified Atkins diet maintained a seizure-free period without antiseizure medications and normal cognitive development in the follow-up period. Our report summarizes the clinical features of GLUT1 syndromes and discusses the importance of early identification and molecular confirmation of GLUT1DS as a treatable metabolic disorder.

Keywords: early diagnosis; genotype; ketogenic diet; myoclonic epilepsy; phenotype.

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Conflict of interest statement

The authors declare no conflict of interest.

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References

1. Klepper J. Glucose Transporter Deficiency Syndrome (GLUT1DS) and the Ketogenic Diet. Epilepsia. 2008;49:46–49. doi: 10.1111/j.1528-1167.2008.01833.x. - DOI - PubMed
1. Koch H., Weber Y.G. The Glucose Transporter Type 1 (Glut1) Syndromes. Epilepsy Behav. 2019;91:90–93. doi: 10.1016/j.yebeh.2018.06.010. - DOI - PubMed
1. Wang D., Pascual J.M., De Vivo D. Glucose Transporter Type 1 Deficiency Syndrome. In: Adam M.P., Ardinger H.H., Pagon R.A., Wallace S.E., Bean L.J.H., Mirzaa G., Amemiya A., editors. GeneReviews®. University of Washington; Seattle, WA, USA: 1993. - PubMed
1. Castellotti B., Ragona F., Freri E., Solazzi R., Ciardullo S., Tricomi G., Venerando A., Salis B., Canafoglia L., Villani F., et al. Screening of SLC2A1 in a Large Cohort of Patients Suspected for Glut1 Deficiency Syndrome: Identification of Novel Variants and Associated Phenotypes. J. Neurol. 2019;266:1439–1448. doi: 10.1007/s00415-019-09280-6. - DOI - PubMed
1. De Vivo D.C., Trifiletti R.R., Jacobson R.I., Ronen G.M., Behmand R.A., Harik S.I. Defective Glucose Transport across the Blood-Brain Barrier as a Cause of Persistent Hypoglycorrhachia, Seizures, and Developmental Delay. N. Engl. J. Med. 1991;325:703–709. doi: 10.1056/NEJM199109053251006. - DOI - PubMed

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[1] Klepper J. Glucose Transporter Deficiency Syndrome (GLUT1DS) and the Ketogenic Diet. Epilepsia. 2008;49:46–49. doi: 10.1111/j.1528-1167.2008.01833.x. - DOI - PubMed

[2] Klepper J. Glucose Transporter Deficiency Syndrome (GLUT1DS) and the Ketogenic Diet. Epilepsia. 2008;49:46–49. doi: 10.1111/j.1528-1167.2008.01833.x. - DOI - PubMed

[3] Koch H., Weber Y.G. The Glucose Transporter Type 1 (Glut1) Syndromes. Epilepsy Behav. 2019;91:90–93. doi: 10.1016/j.yebeh.2018.06.010. - DOI - PubMed

[4] Koch H., Weber Y.G. The Glucose Transporter Type 1 (Glut1) Syndromes. Epilepsy Behav. 2019;91:90–93. doi: 10.1016/j.yebeh.2018.06.010. - DOI - PubMed

[5] Wang D., Pascual J.M., De Vivo D. Glucose Transporter Type 1 Deficiency Syndrome. In: Adam M.P., Ardinger H.H., Pagon R.A., Wallace S.E., Bean L.J.H., Mirzaa G., Amemiya A., editors. GeneReviews®. University of Washington; Seattle, WA, USA: 1993. - PubMed

[6] Wang D., Pascual J.M., De Vivo D. Glucose Transporter Type 1 Deficiency Syndrome. In: Adam M.P., Ardinger H.H., Pagon R.A., Wallace S.E., Bean L.J.H., Mirzaa G., Amemiya A., editors. GeneReviews®. University of Washington; Seattle, WA, USA: 1993. - PubMed

[7] Castellotti B., Ragona F., Freri E., Solazzi R., Ciardullo S., Tricomi G., Venerando A., Salis B., Canafoglia L., Villani F., et al. Screening of SLC2A1 in a Large Cohort of Patients Suspected for Glut1 Deficiency Syndrome: Identification of Novel Variants and Associated Phenotypes. J. Neurol. 2019;266:1439–1448. doi: 10.1007/s00415-019-09280-6. - DOI - PubMed

[8] Castellotti B., Ragona F., Freri E., Solazzi R., Ciardullo S., Tricomi G., Venerando A., Salis B., Canafoglia L., Villani F., et al. Screening of SLC2A1 in a Large Cohort of Patients Suspected for Glut1 Deficiency Syndrome: Identification of Novel Variants and Associated Phenotypes. J. Neurol. 2019;266:1439–1448. doi: 10.1007/s00415-019-09280-6. - DOI - PubMed

[9] De Vivo D.C., Trifiletti R.R., Jacobson R.I., Ronen G.M., Behmand R.A., Harik S.I. Defective Glucose Transport across the Blood-Brain Barrier as a Cause of Persistent Hypoglycorrhachia, Seizures, and Developmental Delay. N. Engl. J. Med. 1991;325:703–709. doi: 10.1056/NEJM199109053251006. - DOI - PubMed

[10] De Vivo D.C., Trifiletti R.R., Jacobson R.I., Ronen G.M., Behmand R.A., Harik S.I. Defective Glucose Transport across the Blood-Brain Barrier as a Cause of Persistent Hypoglycorrhachia, Seizures, and Developmental Delay. N. Engl. J. Med. 1991;325:703–709. doi: 10.1056/NEJM199109053251006. - DOI - PubMed

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GLUT1 Deficiency Syndrome-Early Treatment Maintains Cognitive Development? (Literature Review and Case Report)

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GLUT1 Deficiency Syndrome-Early Treatment Maintains Cognitive Development? (Literature Review and Case Report)

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Abstract

Conflict of interest statement

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