ArticleEpilepsia2023
The presence and severity of epilepsy coincide with reduced γ-aminobutyrate and cortical excitatory markers in succinic semialdehyde dehydrogenase deficiency.
Article in Epilepsia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Central Dysmyelination in SSADH-Deficient Humans and Mice.Annals of clinical and translational neurology · 2025Observational
- Imaging Epilepsy: Past, Passing, and to Come.Epilepsy currents · 2025Review
- The neuropsychological profile of SSADH deficiency, a neurotransmitter disorder of GABA metabolism.Molecular genetics and metabolism · 2025Article
- A crucial active site network of titratable residues guides catalysis and NADProtein science : a publication of the Protein Society · 2025Article
- Inherited metabolic epilepsies-established diseases, new approaches.Epilepsia open · 2024Review
- Clinical features and ALDH5A1 gene findings in 13 Chinese cases with succinic semialdehyde dehydrogenase deficiency.BMC medical genomics · 2024Article
- Consensus guidelines for the diagnosis and management of succinic semialdehyde dehydrogenase deficiency.Molecular genetics and metabolism · 2024Article
- Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder.Journal of neurodevelopmental disorders · 2024Article
- The neurology of creativity: 2023 Hower lecture.Annals of the Child Neurology Society · 2024Review
- ALDH5A1-deficient iPSC-derived excitatory and inhibitory neurons display cell type specific alterations.Neurobiology of disease · 2024Article
- Phenotypic correlates of structural and functional protein impairments resultant from ALDH5A1 variants.Human genetics · 2023Article
- Clinical and biochemical footprints of inherited metabolic diseases. XV. Epilepsies.Molecular genetics and metabolism · 2023Review
- Reduced evoked cortical beta and gamma activity and neuronal synchronization in succinic semialdehyde dehydrogenase deficiency, a disorder of γ-aminobutyric acid metabolism.Brain communications · 2023Article
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Authors and funding
16 authors at 7 institutions in 5 countries.
Funding
Abstract
objectiveSuccinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare inherited metabolic disorder caused by a defect of γ-aminobutyrate (GABA) catabolism. Despite the resultant hyper-GABAergic environment facilitated by the metabolic defect, individuals with this disorder have a paradoxically high prevalence of epilepsy. We aimed to study the characteristics of epilepsy in SSADHD and its concordance with GABA-related metabolites and neurophysiologic markers of cortical excitation.
methodsSubjects in an international natural history study of SSADHD underwent clinical assessments, electroencephalography, transcranial magnetic stimulation (TMS), magnetic resonance spectroscopy for GABA/N-acetyl aspartate quantification, and plasma GABA-related metabolite measurements.
resultsA total of 61 subjects with SSADHD and 42 healthy controls were included in the study. Epilepsy was present in 49% of the SSADHD cohort. Over time, there was an increase in severity in 33% of the subjects with seizures. The presence of seizures was associated with increasing age (p = .001) and lower levels of GABA (p = .002), γ-hydroxybutyrate (GHB; p = .004), and γ-guanidinobutyrate (GBA; p = .003). Seizure severity was associated with increasing age and lower levels of GABA-related metabolites as well as lower TMS-derived resting motor thresholds (p = .04). The cutoff values with the highest discriminative ability to predict seizures were age > 9.2 years (p = .001), GABA < 2.57 μmol·L SIGNIFICANCE: Epilepsy is highly prevalent in SSADHD, and its onset and severity correlate with an age-related decline in GABA and GABA-related metabolite levels as well as TMS markers of reduced cortical inhibition. The reduction of GABAergic activity in this otherwise hyper-GABAergic disorder demonstrates a concordance between epileptogenesis and compensatory responses. These findings may furthermore inform the timing of molecular interventions for SSADHD.
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