ArticleEuropean journal of human genetics : EJHG2013
Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.
Article in European journal of human genetics : EJHG, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 126 citations in OpenAlex.
- Biosynthetic and genetic pathways related to sialic acid metabolism.The Journal of biological chemistry · 2026Review
- Mapping ST3GAL transferase specificities in the glycosylation landscape of N/TERT-1 keratinocytes using Glycogenomics and mass spectrometry.Glycobiology · 2026Article
- Sialylation in the nervous system: Functions and mechanisms.The Journal of biological chemistry · 2026Review
- Serum metabolomics identifies ganglioside dysregulation and pyruvate dehydrogenase complex-related metabolic disturbances in pediatric drug-resistant epilepsy.Frontiers in pediatrics · 2026Article
- Mitochondrial dysfunction and NLRP3 inflammasome activation in drug-resistant epilepsy: emerging insights and mitochondrial-targeted therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- When ganglioside pathways go awry: congenital disorders and experimental insights.Journal of human genetics · 2025Review
- Metabolic and Structural Consequences of GM3 Synthase Deficiency: Insights from an HEK293-T Knockout Model.Biomedicines · 2025Article
- Dynamic glycosylation remodeling in neurological disorders.Frontiers in molecular neuroscience · 2025Review
- Human genetic defects of sphingolipid synthesis.Journal of inherited metabolic disease · 2025Review
- Identification of a novel ST3GAL5 variant in a Chinese boy with GM3 synthase deficiency and literature review of variants in the ST3GAL5 gene.Orphanet journal of rare diseases · 2024Review
- Mechanistic and Therapeutic Implications of Protein and Lipid Sialylation in Human Diseases.International journal of molecular sciences · 2024Review
- Limited impact of cancer-derived gangliosides on anti-tumor immunity in colorectal cancer.Glycobiology · 2024Article
- Dietary gangliosides rescue GM3 synthase deficiency outcomes in mice accompanied by neurogenesis in the hippocampus.Frontiers in neuroscience · 2024Article
- Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis.Glia · 2024Article
- Neural-specific alterations in glycosphingolipid biosynthesis and cell signaling associated with two human ganglioside GM3 synthase deficiency variants.Human molecular genetics · 2023Article
- Synthetic GM1 improves motor and memory dysfunctions in mice with monoallelic or biallelic disruption of GM3 synthase.FEBS open bio · 2023Article
- Rescue of GM3 synthase deficiency by spatially controlled, rAAV-mediated ST3GAL5 delivery.JCI insight · 2023Article
- Whole Exome Sequencing Reveals a Novel Homozygous Variant in the Ganglioside Biosynthetic Enzyme,Genes · 2023Article
- Gangliosides in Neurodegenerative Diseases.Advances in neurobiology · 2023Article
- Functional Impairment of the Nervous System with Glycolipid Deficiencies.Advances in neurobiology · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 8 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
We report two children, born from consanguineous parents, who presented with early-onset refractory epilepsy associated with psychomotor delay, failure to thrive, blindness and deafness. Polarographic and spectrophotometric analyses in fibroblasts and liver revealed a respiratory chain (RC) dysfunction. Surprisingly, we identified a homozygous nonsense mutation in the GM3 synthase gene by using exome sequencing. GM3 synthase catalyzes the formation of GM3 ganglioside from lactosylceramide, which is the first step in the synthesis of complex ganglioside species. Mass spectrometry analysis revealed that the complete absence of GM3 ganglioside and its biosynthetic derivatives was associated with an upregulation of the alternative globoside pathway in fibroblasts. The accumulation of Gb3 and Gb4 globosides likely has a role in RC dysfunction and in the decrease of mitochondrial membrane potential leading to apoptosis, which we observed in fibroblasts. We show for the first time that GM3 synthase deficiency, responsible for early-onset epilepsy syndrome, leads to a secondary RC dysfunction. Our study highlights the role of secondary mitochondrial disorders that can interfere with the diagnosis and the evolution of other metabolic diseases.
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