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GLUT-1DS resistant to ketogenic diet: from clinical feature to in silico analysis. An exemplificative case report with a literature review

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Abstract

Glucose transporter type 1 deficiency syndrome (GLUT-1DS) is characterized by alterations in glucose translocation through the blood–brain barrier (BBB) due to mutation involving the GLUT-1 transporter. The fundamental therapy is ketogenic diet (KD) that provide an alternative energetic substrate — ketone bodies that across the BBB via MCT-1 — for the brain. Symptoms are various and include intractable seizure, acquired microcephalia, abnormal ocular movement, movement disorder, and neurodevelopment delay secondary to an energetic crisis for persistent neuroglycopenia. KD is extremely effective in controlling epileptic seizures and has a positive impact on movement disorders and cognitive impairment. Cases of KD resistance are rare, and only a few of them are reported in the literature, all regarding seizure. Our study describes a peculiar case of GLUT-1DS due to a new deletion involving the first codon of SLC2A1 gene determining a loss of function with a resistance to KD admitted to hospital due to intractable episodes of dystonia. This patient presented a worsening of symptomatology at higher ketonemia values but without hyperketosis and showed a complete resolution of symptomatology while maintaining low ketonemia values. Our study proposes an in-silico genomic and proteomic analysis aimed at explaining the atypical response to KD exhibited by our patient. In this way, we propose a new clinical and research approach based on precision medicine and molecular modelling to be applied to patients with GLUT-1DS resistant to first-line treatment with ketogenic diet by in silico study of genetic and altered protein product.

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Authors and Affiliations

  1. Neonatal Intensive Care Unit and Neonatal Accompaniment Unit, Azienda Ospedaliero-Universitaria Policlinico “Rodolico-San Marco,” San Marco Hospital, University of Catania, Catania, Italy

    Raffaele Falsaperla

  2. Unit of Pediatrics and Pediatric Emergency, Azienda Ospedaliero-Universitaria Policlinico, “Rodolico-San Marco,” San Marco Hospital, Catania, Italy

    Raffaele Falsaperla, Vincenzo Sortino & Giovanna Vitaliti

  3. Unit of Math and Comp Science, Department of Clinical and Experimental Medicine, Catania, Italy

    Grete Francesca Privitera

  4. Unit of Clinical Pediatrics, Department of Clinical and Experimental Medicine, University of Catania, AOU “Policlinico,” PO “G. Rodolico”, Via S. Sofia, 78, 95124, Catania, Italy

    Martino Ruggieri

  5. Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Catania, Italy

    Gaia Fusto & Xena Giada Pappalardo

  6. National Council of Research, Institute for Research and Biomedical Innovation (IRIB), Unit of Catania, Catania, Italy

    Xena Giada Pappalardo

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  1. Raffaele Falsaperla
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Correspondence to Raffaele Falsaperla.

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Ethics approval and consent to participate

The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki and approved by ethics committee of the University of Catania, Italy (Ethical Committee Catania 1 Clinical Registration n. 180/2023/PO). Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

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Written informed consent was obtained from the patient’s legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

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The authors declare no competing interests.

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Falsaperla, R., Sortino, V., Vitaliti, G. et al. GLUT-1DS resistant to ketogenic diet: from clinical feature to in silico analysis. An exemplificative case report with a literature review. Neurogenetics (2024). https://doi.org/10.1007/s10048-023-00742-8

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