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)

The patient developed myoclonic seizures at 3 months of age and his hair demonstrated the pili torti pattern. The low serum copper content and ceruloplasmin confirmed the diagnosis of Menkes disease. The characteristic signs on the images were: high echo level regions in the cerebrum as detected by brain ultrasonography, low density areas of white matter detected by CT scan, and low signal intensities of white matter by both T1 and balanced MR images.
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PMID:Serial imaging of Menkes disease. 218 34

Kinky hair disease, first described in 1962, is a sex-linked disorder, with its gene located on the long arm of the X chromosome close to the centromere. The condition is marked by intellectural deterioration, seizures, and poorly pigmented, friable hair. Bony changes, resembling scurvy, tortuosities of the cerebral and systemic vasculature, and diverticuli of the bladder are also seen. Biochemically, the most diagnostic alteration is a marked reduction in blood copper and ceruloplasmin levels. The mechanism for the low serum copper has not been defined. Even though parental copper administration will correct the biochemical abnormalities, such treatment will not arrest cerebral deterioration.
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PMID:Kinky hair disease: twenty five years later. 283 49

The recognition of Menkes' kinky hair syndrome, trichopoliodystrophy, may present problems in the early neonatal period. The serum copper, and ceruloplasmin levels are within the range of normal infants in the first week of life; they are higher than normal in the cord blood of affected infants and fall gradually. Pili torti may only develop later, as the primary fetal hair is normal. The baby may appear bald, or both normal and abnormal hair may be found in different areas of the skull. The roentgenographic signs of wormian bones in the skull, metaphyseal spurring of the long bones, and diverticuli of the bladder develop progressively and may not be seen until after 6 weeks of age. However, diagnosis is possible in the neonatal period, if male infants with unexplained hypothermia, hypotonia, septicemia, or seizures are investigated by serum copper and ceruloplasmin levels after 1 month of age.
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PMID:Difficulties in the neonatal diagnosis of Menkes' kinky hair syndrome--trichopoliodystrophy. 646 87

The authors report a case of Menkes' syndrome, probably the first one described in Brazil. The patient, a 15-month-old boy, showed pili torti, early progressive psychomotor deterioration and seizures. Serum levels of ceruloplasmin and copper were very low. Neuroradiological and roentgenological examinations revealed diffuse cerebral atrophy, arterial changes and bone abnormalities. At the post-mortem examination the more consistent findings were cerebral atrophy, neuronal loss in the thalamus and above all cerebellar cortical lesions. The disease has a sex-linked recessive inheritance and is believed to be caused by an inborn error of copper metabolism, perhaps subordinated to changes of proteins which carry copper to different tissues. The relevant literature in relation to the pathogenesis is reviewed.
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PMID:[Menkes syndrome: review of the pathogenesis apropos of a clinico-pathological case]. 649 17

The effect of phenytoin (PHT) on the metabolism of zinc (Zn) and copper (Cu) has been studied during treatment for epilepsy. Eleven previously untreated epileptics were followed from the start of therapy together with 20 patients on long-term therapy. In eight untreated epileptic males low serum concentrations of Zn (S-Zn) were found. At the start of therapy increased S-Zn and S-Cu concentrations were noted. After 1 month of therapy S-Zn was at pretherapy levels but S-Cu was still increased. No changes in the urinary excretion of the metals or in the CSF-Zn concentrations were registered. In the patients on long-term therapy S-Zn was unchanged while S-Cu and S-ceruloplasmin were increased significantly compared with age- and sex-matched controls. It is postulated that the drug may cause a relative zinc deficiency through a chelate binding between Zn and PHT and/or an increased absorption and accumulation of Cu. These effects may be of importance in the development of intoxication symptoms and may also influence the effectiveness of seizure control.
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PMID:Zinc and copper metabolism in phenytoin therapy. 714 Jun 61

We studied 2 of 4 affected boys with a new disease associated with abnormalities of copper metabolism. The four cases occurred in two generations of a family. This syndrome was similar to Menkes disease in some respects: X-linked recessive inheritance, marked psychomotor retardation with seizures, low serum copper and ceruloplasmin levels, and a block in gut copper absorption. There were also striking differences from Menkes disease. Patients had normal birthweight at term, no hypothermia, and survived beyond the usual Menkes age group with static neurologic disease including hypotonia and choreoathetosis. In addition, general examination of both children was unremarkable apart from undescended testes and growth retardation. The hair, facies, and skin were normal and there was no radiologic evidence of bony changes. Detailed studies of copper absorption were performed.
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PMID:An X-linked disease of the nervous system with disordered copper metabolism and features differing from Menkes disease. 719 7

Epilepsy is a dominant trait in EL mice, a model for human complex partial seizures. We recently mapped the major gene, El-1, to chromosome 9 near the predicted location for the ceruloplasmin (Cp) gene. We now present evidence for a partial duplication in the Cp gene in EL mice. This Cp duplication is coinherited with seizures in backcross generations and is associated with enhanced expression of Cp mRNA and increased Cp oxidase activity. Moreover, the duplication is associated with an enhanced frequency of double recombinants, simulating negative interference. The findings are relevant to the basic mechanisms of epilepsy and to theories of genetic recombination and gene mapping.
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PMID:Ceruloplasmin gene defect associated with epilepsy in EL mice. 1245 59

Occipital horn syndrome (OHS, Ehlers-Danlos syndrome type IX) belongs to the category of the copper metabolism disorders and is at present being investigated biochemically as is Menkes' disease. Unlike Menkes' disease, most patients with OHS have mild submentality. We report a case of OHS with severe central nervous system involvement and muscular atrophy in a 34-year-old male. He had psychomotor retardation and seizures since early childhood and now presented severe mental retardation and generalized muscular atrophy in addition to characteristic facial appearance, hyperelasticity of the skin and joint subluxation. Laboratory investigations revealed a low serum copper and ceruloplasmin level as well as intestinal non-absorption of copper. Radiographic imaging showed occipital exostoses, bladder diverticula, tortuosity of the peripheral vein and osteoporosis of the skeletal bones. The activity of lysyl oxidase, a copper-enzyme involved in cross-link formation in collagen, was found to be decreased in a skin-biopsy specimen. Electron-microscopic investigation of a muscle biopsy showed irregularity of the myofibrillar network and accumulation of concentric laminated bodies in the subsarcolemmal regions.
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PMID:Central nervous system involvement and generalized muscular atrophy in occipital horn syndrome: Ehlers-Danlos type IX. A first Japanese case. 809 5

To delineate further the clinical spectrum of Menkes disease, an X-linked recessive disorder of copper transport, we studied 4 related males, ranging in age from 4-38 years, with a unique phenotype that combines manifestations of classical and mild Menkes disease and occipital horn syndrome (OHS). The propositus, and 18-year-old man, was evaluated following an intracerebral hemorrhage at age 15 years and was noted to have marked hypotonia, motor delay with mental retardation, bladder diverticula, failure to thrive, and diarrhea from infancy; seizures from age 3 years; and abnormal hair (pili torti) and face, cutis laxa, and multiple joint dislocations. Radiographic abnormalities included occipital exostoses, tortuous cerebral blood vessels with multiple branch occlusions, and hammer-shaped clavicles. Biochemical studies demonstrated reduced copper and ceruloplasmin levels in serum, and abnormal plasma catecholamine ratios. We reported previously the molecular defect in this family, a splice-site mutation that predicts formation of approximately 20% of the normal Menkes gene product [Kaler et al., 1994: Nat Genet 18:195-202]. Here, we detail the clinical course and physical features and radiographic findings in these 4 individuals, and compare their phenotype with classical and mild Menkes and OHS. Unusual Menkes disease variants such as this may escape recognition due to anomalies that appear inconsistent with the diagnosis, particularly prolonged survival and later onset of seizures. Males with mental retardation and connective tissue abnormalities should be evaluated for biochemical evidence of defective copper transport.
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PMID:Distinctive Menkes disease variant with occipital horns: delineation of natural history and clinical phenotype. 891 40

For the development of new drugs for hitherto untreatable epilepsy, it is necessary to clarify the basic pathophysiology involved in such epileptic seizures and find the target site. This review focused on molecular events related to the expression and expansion of the epileptic focus which are the target of novel antiepileptics. Immediate early genes such as c-fos followed by expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been evidenced as initial important phenomena in the cascade of molecular systems that develop and complement the transient neuronal excitation to long-term neuronal plasticity. Non-receptor type tyrosine kinase Fyn in the Src family has been suggested to promote kindling development via tyrosine phosphorylation of the NMDA-receptor subunit, NR2B. The cause of abnormality in the inhibitory system is induced by lowering of glutamate-dependent GABA release in the epileptic focus within the hippocampus in human temporal epilepsy. This is probably attributed to a decrease in GABA transporters. Regarding abnormality of the excitatory system, there is an increase in glutamate release prior to convulsive seizures, an enhancement of NMDA receptor responsiveness and high levels of AMPA receptors related to convulsion after completion of kindling. In gene analysis of human familiar epilepsy, abnormalities and point mutations have recently been found in the following genes: KCNQ 2 and KCNQ3, coding for K+ channels; CHRNA4 of the nicotinic receptor subunit alpha 4; and the cystatin B gene. In epilepsy model mice, EL mice with several gene mutations known to be involved in the seizures, the El-1 gene contains an abnormality of the ceruloplasmin gene. SER (spontaneously epileptic rat: zi/zi, tm/tm), a double mutant, manifests a deletion of the region containing the aspartoacylase gene related to the tm gene. Since an increase in N-acetyl-L-aspartate (NAA) is observed in the SER brain, NAA may serve to evoke seizures.
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PMID:[Molecular mechanism underlying epileptic seizure: forwards development of novel drugs for untreatable epilepsy]. 1055 79


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