ArticleHuman molecular genetics2020
A novel mouse model for pyridoxine-dependent epilepsy due to antiquitin deficiency.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Review
- Astrocytes in Genetic Epilepsies: Supporting Actor or Key Player?Journal of neuroscience research · 2026Review
- Astrocyte redox imbalance underlies prelimbic neuronal hypoactivity and maladaptive affective behaviors in epilepsy.Science advances · 2026Article
- Classical and Emerging Biomarkers in Pyridoxine-Dependent Epilepsy (PDE-ALDH7A1): Implications for Early Diagnosis and Therapeutic Development.Biomolecules · 2026Review
- Targeting AASS alleviates neurotoxicity and improves mitochondrial function in astrocyte models for pyridoxine-dependent epilepsy.Molecular therapy. Nucleic acids · 2025Article
- Lactic acidosis, rhabdomyolysis, and hyperammonemia: Atypical presentation in a new patient with PDE-ALDH7A1 defect.Molecular genetics and metabolism reports · 2025Article
- Diverse species of animal models in epilepsy research: Progress and perspectives.Zoological research · 2025Review
- Vitamin K as an add-on therapy in pyridoxine-dependent epilepsy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Dysregulation of astrocyte-derived matrix gla protein impairs dendritic spine development in pyridoxine-dependent epilepsy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- New treatment for pyridoxine-dependent epilepsy due to ALDH7A1 deficiency: first proof-of-principle of upstream enzyme inhibition in the mouse.Brain communications · 2025Article
- LysineFrontiers in molecular neuroscience · 2025Review
- Assessment of urinary 6-oxo-pipecolic acid as a biomarker for ALDH7A1 deficiency.Journal of inherited metabolic disease · 2025Article
- Analysis of clinical features and genetic variants in Chinese children with pyridoxine-dependent epilepsy: a case series study.Frontiers in neurology · 2025Article
- Partial suppression of BCAA catabolism as a potential therapy for BCKDK deficiency.Molecular genetics and metabolism reports · 2024Article
- Disrupted de novo pyrimidine biosynthesis impairs adult hippocampal neurogenesis and cognition in pyridoxine-dependent epilepsy.Science advances · 2024Article
- Pyridoxine-dependent epilepsy: Current perspectives and questions for future research.Annals of the Child Neurology Society · 2023Article
- Clocking Epilepsies: A Chronomodulated Strategy-Based Therapy for Rhythmic Seizures.International journal of molecular sciences · 2023Review
- Metabolomics analysis of antiquitin deficiency in cultured human cells and plasma: Relevance to pyridoxine-dependent epilepsy.Journal of inherited metabolic disease · 2023Article
- Global Metabolomics Discovers Two Novel Biomarkers in Pyridoxine-Dependent Epilepsy Caused by ALDH7A1 Deficiency.International journal of molecular sciences · 2022Article
- The Metabolite Saccharopine Impairs Neuronal Development by Inhibiting the Neurotrophic Function of Glucose-6-Phosphate Isomerase.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disease caused by mutations in the ALDH7A1 gene leading to blockade of the lysine catabolism pathway. PDE is characterized by recurrent seizures that are resistant to conventional anticonvulsant treatment but are well-controlled by pyridoxine (PN). Most PDE patients also suffer from neurodevelopmental deficits despite adequate seizure control with PN. To investigate potential pathophysiological mechanisms associated with ALDH7A1 deficiency, we generated a transgenic mouse strain with constitutive genetic ablation of Aldh7a1. We undertook extensive biochemical characterization of Aldh7a1-KO mice consuming a low lysine/high PN diet. Results showed that KO mice accumulated high concentrations of upstream lysine metabolites including ∆1-piperideine-6-carboxylic acid (P6C), α-aminoadipic semialdehyde (α-AASA) and pipecolic acid both in brain and liver tissues, similar to the biochemical picture in ALDH7A1-deficient patients. We also observed preliminary evidence of a widely deranged amino acid profile and increased levels of methionine sulfoxide, an oxidative stress biomarker, in the brains of KO mice, suggesting that increased oxidative stress may be a novel pathobiochemical mechanism in ALDH7A1 deficiency. KO mice lacked epileptic seizures when fed a low lysine/high PN diet. Switching mice to a high lysine/low PN diet led to vigorous seizures and a quick death in KO mice. Treatment with PN controlled seizures and improved survival of high-lysine/low PN fed KO mice. This study expands the spectrum of biochemical abnormalities that may be associated with ALDH7A1 deficiency and provides a proof-of-concept for the utility of the model to study PDE pathophysiology and to test new therapeutics.
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