Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate Shuttle-Related Encephalopathy

Early-infantile encephalopathies with epilepsy are devastating conditions mandating an accurate diagnosis to guide proper management. Whole-exome sequencing was used to investigate the disease etiology in four children from independent families with intellectual disability and epilepsy, revealing bi-allelic GOT2 mutations. In-depth metabolic studies in individual 1 showed low plasma serine, hypercitrullinemia, hyperlactatemia, and hyperammonemia. The epilepsy was serine and pyridoxine responsive.
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research

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Publication date: November 2019Source: Epilepsy &Behavior, Volume 100, Part AAuthor(s): Florentina M.E. Pinckaers, Mebeline E. Boon, Marian H.J.M. MajoieAbstractPurposeWhile levetiracetam (LEV) usage is a known risk factor for psychosis in epilepsy, the modulating effect of certain patient and treatment characteristics on the risk of psychosis has yet to be fully elucidated.MethodsIn our tertiary epilepsy center, 84 patients with psychotic symptoms during LEV usage and 100 controls without psychotic symptoms during LEV usage were selected. Patient records were reviewed including demographics, medical history, antiepile...
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
Abstract PURPOSE: While levetiracetam (LEV) usage is a known risk factor for psychosis in epilepsy, the modulating effect of certain patient and treatment characteristics on the risk of psychosis has yet to be fully elucidated. METHODS: In our tertiary epilepsy center, 84 patients with psychotic symptoms during LEV usage and 100 controls without psychotic symptoms during LEV usage were selected. Patient records were reviewed including demographics, medical history, antiepileptic drug use, and cognitive abilities. Univariate comparisons were performed, and variables with p 
Source: Epilepsy and Behaviour - Category: Neurology Authors: Tags: Epilepsy Behav Source Type: research
AbstractThe lack of cerebral creatine (Cr) causes intellectual disability and epilepsy. In addition, a significant portion of individuals with Cr transporter (Crt) deficiency (CTD), the leading cause of cerebral Cr deficiency syndromes (CCDS), are diagnosed with attention-deficit hyperactivity disorder. While the neurological effects of CTD are clear, the mechanisms that underlie these deficits are unknown. Part of this is due to the heterogenous nature of the brain and the unique metabolic demands of specific neuronal systems. Of particular interest related to Cr physiology are dopaminergic neurons, as many CCDS patients ...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research
Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome characterized by bilateral myoclonic and tonic-clonic seizures typically starting in adolescence and responding well to medication. Misdiagnosis of a more severe progressive myoclonus epilepsy (PME) as JME has been suggested as a cause of drug-resistance. Medical records of the Epilepsy Center Hessen-Marburg between 2005 and 2014 were automatically selected using keywords and manually reviewed regarding the presence of a JME diagnosis at any timepoint. The identified patients were evaluated regarding seizure outcome and drug resistance according to ILAE criter...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
This study showed evidence that BRV may be an effective adjunctive therapy in patients with drug-resistant focal or generalized epilepsies whose seizures have previously not responded or tolerated LEV therapy. We demonstrated a higher incidence of treatment-emergent AEs leading to lower retention rates compared with previous studies across all patient groups. There were, however, no significant differences in tolerability between patients with preexisting psychiatric or behavioral comorbidities, or intellectual disability to those without.
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
(The American Journal of Human Genetics 105, 413 –424; August 1, 2019)
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Correction Source Type: research
CONCLUSION: Whole-exome sequencing and EP are the most cost-effective genetic tests for epilepsy. Our analyses support for a broad population of patients with unexplained epilepsy, starting with these tests. Although less expensive, CMA has lower yield, and its use as the first-tier test is thus not supported from a cost-effectiveness perspective. PMID: 31476917 [PubMed - as supplied by publisher]
Source: Epilepsy Currents - Category: Neurology Tags: Epilepsy Curr Source Type: research
This study showed evidence that BRV may be an effective adjunctive therapy in patients with drug-resistant focal or generalized epilepsies whose seizures have previously not responded or tolerated LEV therapy. We demonstrated a higher incidence of treatment-emergent AEs leading to lower retention rates compared with previous studies across all patient groups. There were, however, no significant differences in tolerability between patients with preexisting psychiatric or behavioral comorbidities, or intellectual disability to those without. PMID: 31493736 [PubMed - as supplied by publisher]
Source: Epilepsy and Behaviour - Category: Neurology Authors: Tags: Epilepsy Behav Source Type: research
Abstract PURPOSE OF REVIEW: It is widely accepted that childhood convulsive status epilepticus (CSE) has associated short-term and long-term mortality and morbidity. However, the role of CSE itself on subsequent adverse outcomes is still debated. In addition, whether prolonged seizures cause any long-term hippocampal injury and developmental or memory impairment is uncertain. In this review, we aim to provide an overview of long-term outcomes after childhood CSE, highlighting data from recent literature on this subject. RECENT FINDINGS: Long-term outcome after childhood CSE is favorable in previously normal c...
Source: Epilepsy Curr - Category: Neurology Authors: Tags: Curr Opin Pediatr Source Type: research
Conclusions: Our experience suggests that intranasal dexmedetomidine is an advantageous sedation option for children and adults with intractable epilepsy who are undergoing MEG. Further research is needed to determine the best ways to apply these methods to younger children and those with developmental disabilities.
Source: Journal of Clinical Neurophysiology - Category: Neurology Tags: Original Research Source Type: research
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