Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Very young children with organic brain damage, intractable seizures, and developmental retardation are at particular risk of developing fatal hepatic dysfunction coincident with valproate therapy, especially if the children are also receiving other anticonvulsant drugs. The mechanism of valproate-associated hepatic failure in these children is unclear. There are two major theories of etiology. The first concerns the manyfold consequences of depletion of CoA due to sequestration into poorly metabolized valproyl CoA and valproyl CoA metabolites. The other theory proposes that the unsaturated valproate derivative 2-n-propyl-4-pentenoic acid and/or metabolically activated intermediates are toxic and directly cause irreversible inhibition of enzymes of beta-oxidation. The present study shows for the first time that in developing mice, when panthothenic acid and carnitine are administered with valproate, at least some of the effects of valproate are mitigated. Perhaps most importantly, the beta-hydroxybutyrate concentration in plasma and the free CoA and acetyl CoA levels in liver do not fall so low. Cotreatment with carnitine alone was without effect. Findings support the CoA depletion mechanism of valproate inhibition of beta-oxidation and other CoA- and acetyl CoA-requiring enzymic reactions and stress the role of carnitine in the regulation of CoA synthesis at the site of action of pantothenate kinase.
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PMID:Amelioration of adverse effects of valproic acid on ketogenesis and liver coenzyme A metabolism by cotreatment with pantothenate and carnitine in developing mice: possible clinical significance. 157 Feb 10

We describe a 24-year-old Japanese woman with pantothenate kinase-associated neurodegeneration (PKAN) whose only early symptom was postural tremor in the right hand at around 18 years of age, leading to a diagnosis of essential tremor at age 21. Although she was treated with arotinolol hydrochloride and clonazepam, she gradually progressed to extrapyramidal and pyramidal signs several years later. T2-weighted magnetic resonance images (MRI) showed bilaterally marked hypointensity with a central region of hyperintensity in the globus pallidus, or the so-called "eye-of-the-tiger" sign. Six years have passed since the initial appearance of postural tremor, whereas she has not shown choreoathetosis, retinitis pigmentosa, optic atrophy, or seizure. Direct sequencing of the patient's genomic DNA revealed homozygous base substitutions in the pantothenate kinase gene (PANK2): the A764-->G substitution (N245S) due to consanguinity of her parents. Although the heterozygous form of this mutation has already been reported among several families, this is the first report of the homozygous mutation in a patient with atypical-type PKAN. This detailed description of the clinical features of a Japanese patient with PKAN arising from homozygous N245S mutations in PANK2 would be useful for elucidating the pathogenesis of PKAN.
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PMID:Pantothenate kinase-associated neurodegeneration initially presenting as postural tremor alone in a Japanese family with homozygous N245S substitutions in the pantothenate kinase gene. 1546 96

We report a case of a young girl with early onset pantothenate kinase-kssociated neurodegeneration (PKAN) whose initial clinical manifestation was ataxia at the age of 2.5 years. Subsequently the patient presented to us with refractory severe dystonia resulting in essentially complete loss of motor control. She had a mutation in PANK2 gene consisting of an aminoacid change of Alanine to Valine in exon 5 (A382V). After Globus Pallidus deep brain stimulation (DBS) at the age of 11 years, the patient regained useful motor function and speech with a marked decrease in the severity of the dystonia. The patient's condition gradually returned to her pre-DBS status when the device had to be removed 3 months later due to infection. Our case is the sixth case with classical PKAN that was treated by Globus Pallidus stimulation, the fifth one to have a favorable response to it and the only one in whom response was proven by the inadvertent removal of the DBS device due to infection. In addition, our case had a novel mutation and novel clinical features (onset with ataxia, occurrence of early seizure activity) on top of her other symptoms that were otherwise typical of early onset disease.
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PMID:Deep brain stimulation as a mode of treatment of early onset pantothenate kinase-associated neurodegeneration. 1970 16

Neuroacanthocytosis is an inclusive term for a genetically heterogeneous group of disorders characterized by the association of neurological abnormalities with red cell acanthocytosis. In the late 1960s, Levine et al. reported a family with a syndrome of neurological deficits such as choreiform involuntary movements, epileptic seizures, intellectual impairment, and paranoid ideation along with acanthocytosis without any disturbance in either alpha- or beta-lipoproteins nor retinitis pigmentosa. Critchley et al. also reported familial cases with acanthocytosis and neurological disorders without beta-lipoproteinemia. These cases have been classified as the Levine-Critchley syndrome of neuroacanthocytosis. Cases of neuroacanthocytosis have been classified into 2 groups depending on the presence or absence of movement disorders such as chorea. One group comprises the core neuroacanthocytosis syndromes in which neurodegeneration occurs primarily in the basal ganglia, specifically the striatum, causing movement disorders. The core neuroacanthocytosis syndromes mainly comprise of the two diseases, chorea-acanthocytosis and the McLeod syndrome. Huntington's disease-like 2, and pantothenate kinase-associated neurodegeneration (PKAN) are very rare but these diseases can also be included in this group of syndromes. Advances in molecular genetics have enabled us to distinguish between these diseases. Recently, the hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration syndrome (HARP syndrome) has been genetically shown to be an allelic form of PKAN. The second group of neuroacanthocytosis syndromes includes abetalipoproteinemia (Bassen-Kornzweig disease) and hypobetalipoproteinemia that are characterized by the abnormal decay of lipoprotein with the intestinal malabsorption of fat leading to neurological abnormalities and acanthocytosis. In this type of neuroacanthocytosis shows a progressive spinocerebellar ataxia with peripheral neuropathy and retinitis pigmentosa are observed, but movement disorders are not seen.
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PMID:[Neuroacanthocytosis update]. 1856 59

Hallervorden-Spatz syndrome is a disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. The disease is caused by mutations in gene encoding pantothenate kinase 2 (PANK2) and patients have pantothenate kinase-associated neurodegeneration. We present an 8-year-old boy with progressive muscle dystonia, neuroregression, frequent fall and multiple injury marks of different stages. Seizures are rare with PANK2. This child had seizure onset at 4 years of age and seizure free on valproate and levetricetam. The CT scan showed tiger eye appearance and mutations on PANK2 gene.
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PMID:Hallervorden-Spatz Syndrome with Seizures. 2730 11