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Successful treatment of intractable epilepsy with ketogenic diet therapy in twins with ALG3-CDG

  • C. Paketci
    Correspondence
    Corresponding author at: Division of Child Neurology, Department of Pediatrics, Dokuz Eylul University Faculty of Medicine, İzmir, Turkey.
    Affiliations
    Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey
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  • P. Edem
    Affiliations
    Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey
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  • S. Hiz
    Affiliations
    Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey

    Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey
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  • E. Sonmezler
    Affiliations
    Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey

    Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey
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  • D. Soydemir
    Affiliations
    Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey
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  • G. Sarikaya Uzan
    Affiliations
    Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey
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  • Y. Oktay
    Affiliations
    Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey

    Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey

    Department of Medical Biology, School of Medicine, Dokuz Eylul University, Izmir, Turkey
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  • E. O'Heir
    Affiliations
    Center for Mendelian Genomics and Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, United States

    Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, United States
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  • S. Beltran
    Affiliations
    CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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  • S. Laurie
    Affiliations
    CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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  • A. Töpf
    Affiliations
    John Walton Muscular Dystrophy Research Centre, Institute of Translational and Clinical Research, Newcastle University and Newcastle Hospitals, Newcastle upon Tyne, United Kingdom
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  • H. Lochmuller
    Affiliations
    Department of Neuropediatrics and Muscle Disorders, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany

    Centro Nacional de Análisis Genómico (CNAG-CRG), Center for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain

    Children's Hospital of Eastern Ontario Research Institute, Division of Neurology, Department of Medicine, The Ottawa Hospital, and Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada
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  • R. Horvath
    Affiliations
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
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  • U. Yis
    Affiliations
    Department of Paediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir, Turkey
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      Abstract

      Background

      Congenital disorders of glycosylation (CDG) is a heterogeneous group of congenital metabolic diseases with multisystem clinical involvement. ALG3-CDG is a very rare subtype with only 24 cases reported so far.

      Case

      Here, we report two siblings with dysmorphic features, growth retardation, microcephaly, intractable epilepsy, and hemangioma in the frontal, occipital and lumbosacral regions.

      Results

      We studied two siblings by whole exome sequencing. A pathogenic variant in ALG3 (NM_005787.6: c.165C > T; p.Gly55=) that had been previously associated with congenital glycolysis defect type 1d was identified. Their intractable seizures were controlled by ketogenic diet.

      Conclusion

      Although prominent findings of growth retardation and microcephaly seen in our patients have been extensively reported before, presence of hemangioma is a novel finding that may be used as an indication for ALG3-CDG diagnosis. Our patients are the first reported cases whose intractable seizures were controlled with ketogenic diet. This report adds ketogenic diet as an option for treatment of intractable epilepsy in ALG3-CDG.

      Keywords

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