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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A newborn infant exhibiting seizures and spastic tetraparesis at the age of 1 week was shown to excrete excessive quantities of sulphite, taurine, S-sulphocysteine and thiosulphate, characteristic of sulphite oxidase deficiency. In addition, increased renal excretion of xanthine and hypoxanthine combined with a low serum and urinary uric acid was consistent with xanthine dehydrogenase deficiency. Both deficiencies could be established at the enzyme level. The primary defect giving rise to the combined abnormalities is the absence of a molybdenum cofactor, a molybdenum-containing pterin being an essential component of both enzymes. The patient developed a severe neurological syndrome, brain atrophy and lens dislocation and died at the age of 22 months. Attempts at treatment, such as oral administration of ammonium molybdate, sodium sulphate, D-penicillamine, 2-mercaptoethane sulphonic acid, pyridoxine and thiamine did not influence the clinical course.
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PMID:Report on a new patient with combined deficiencies of sulphite oxidase and xanthine dehydrogenase due to molybdenum cofactor deficiency. 321 99

There are many causes of lens dislocation in man. Amongst these are two inborn errors of sulfur amino acid metabolism, viz., homocystinuria and sulfite oxidase deficiency. To date nine patients have been found in whom a combined deficiency of sulfite oxidase and xanthine dehydrogenase was observed. This inherited disease is due to a defective synthesis of molybdenum cofactor, an essential component for the assembly of both enzymes. The main clinical symptoms of these patients were: facial dysmorphic features, severe feeding difficulties, mental retardation, abnormal muscle tone, severe seizures and myoclonia. Four out of nine patients had dislocated eye lenses. The main biochemical findings included hypouricemia, xanthinuria, an increased excretion of sulfite, thiosulfate, S-sulfocysteine, taurine and a decreased excretion of inorganic sulfate. The prognosis of the disease is poor; various attempts at treatment were not successful so far. Prenatal diagnosis by assay of sulfite oxidase in cultured amniotic fluid cells and by direct measurement of amniotic fluid S-sulfocysteine is possible.
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PMID:Absence of hepatic molybdenum cofactor. An inborn error of metabolism associated with lens dislocation. 387 98

Intractable seizures in the neonatal period may be caused by molybdenum-cofactor deficiency, an inborn error which combines the deficiencies of sulphite oxidase and xanthine dehydrogenase. The neurological symptoms of molybdenum cofactor and isolated sulphite oxidase deficiencies are identical. Two new cases are reported, and the literature on neonatal convulsions due to molybdenum-cofactor and sulphite deficiencies is reviewed. Because of the high incidence of neonatal convulsions a search for this deficiency is advocated in each case of unexplained refractory neonatal convulsions. Diagnosis may be missed or delayed on standard metabolic screening for several reasons discussed. By simply using a sulphite strip test in a fresh urine sample an indication for the defect can be obtained. Antenatal diagnosis can be performed by assay of sulphite oxidase activity in a chorionic villus sample.
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PMID:Molybdenum-cofactor deficiency: an easily missed cause of neonatal convulsions. 835 18

Isolated sulfite oxidase (SO) deficiency is an autosomal recessively inherited inborn error of sulfur metabolism. In this report of a ninth patient the clinical history, laboratory results, neuropathological findings and a mutation in the sulfite oxidase gene are described. The data from this patient and previously published patients with isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are summarized to characterize this rare disorder. The patient presented neonatally with intractable seizures and did not progress developmentally beyond the neonatal stage. Dislocated lenses were apparent at 2 months. There was increased urine excretion of sulfite and S-sulfocysteine and a decreased concentration of plasma cystine. A lactic acidemia was present for 6 months. Liver sulfite oxidase activity was not detectable but xanthine dehydrogenase activity was normal. The boy died of respiratory failure at 32 months. Neuropathological findings of cortical necrosis and extensive cavitating leukoencephalopathy were reminiscent of those seen in severe perinatal asphyxia suggesting an etiology of energy deficiency. A point mutation that resulted in a truncated protein missing the molybdenum-binding site has been identified.
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PMID:Isolated sulfite oxidase deficiency. 905 47

Molybdenum cofactor deficiency (MoCoD) is a fatal disorder manifesting, shortly after birth, with profound neurological abnormalities, mental retardation, and severe seizures unresponsive to any therapy. The disease is a monogenic, autosomal recessive disorder, and the existence of at least two complementation groups suggests genetic heterogeneity. In humans, MoCoD leads to the combined deficient activities of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. By using homozygosity mapping and two consanguineous affected kindreds of Israeli-Arab origin, including five patients, we demonstrated linkage of a MoCoD gene to an 8-cM region on chromosome 6p21.3, between markers D6S1641 and D6S1672. Linkage analysis generated the highest combined LOD-score value, 3.6, at a recombination fraction of 0, with marker D6S1575. These results now can be used to perform prenatal diagnosis with microsatellite markers. They also provide the only tool for carrier detection of this fatal disorder.
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PMID:Localization of a gene for molybdenum cofactor deficiency, on the short arm of chromosome 6, by homozygosity mapping. 963 14

Molybdenum cofactor (MoCo) deficiency leads to a combined deficiency of the molybdo-enzymes sulphite oxidase, xanthine dehydrogenase and aldehyde oxidase. No therapy is known for this rare disease, which results in neonatal seizures and other neurological symptoms identical to sulphite oxidase deficiency. It is inherited autosomal-recessively and leads to early childhood death. Prenatal diagnosis has been performed since 1983 by the measurement of sulphite oxidase activity, but no enzymatic carrier diagnosis is possible. The human genes necessary for MoCo biosynthesis have recently been cloned and mutations in the bicistronic MOCS1 gene could be identified in most European patients. In a Danish family we have now performed enzymatic and molecular genetic analysis in parallel after chorionic villus sampling. The sulphite oxidase activity in uncultured CVS material was found to be normal. A MOCS1 splice site mutation, found homozygous in the affected patient, was found in a heterozygous state in cultured chorionic cells. This confirmed that the fetus was not affected, since heterozygous carriers of a MoCo deficiency allele do not display any symptoms.
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PMID:Molybdenum cofactor deficiency: first prenatal genetic analysis. 1032 49

Molybdenum cofactor (MoCo) deficiency leads to a combined deficiency of the molybdoenzymes sulphite oxidase, xanthine dehydrogenase and aldehyde oxidase. Effective therapy is not available for this rare disease, which results in neonatal seizures and other neurological symptoms identical to those of sulphite oxidase deficiency. It is an autosomal recessive trait and leads to early childhood death. Biosynthesis of MoCo can be divided into the formation of a precursor and its subsequent conversion to the organic moiety of MoCo by molybdopterin synthase. These two steps are the molecular basis of the two observed complementation groups A and B and of two types of MoCo deficiency with an identical phenotype. MOCS1 is defective in the majority of patients (group A) and was shown to encode two enzymes functioning in the formation of a precursor. The corresponding transcript is bicistronic with two consecutive open reading frames (ORFs). MOCS2 encodes the small and large subunits of molybdopterin synthase via a single transcript with two overlapping reading frames. This gene carries lesions in the B complementation group less frequently observed in patients. Both genes, MOCS1 and MOCS2, share the unusual bicistronic architecture, have identical and very low expression profiles and extremely conserved C-terminal ends in their 5'-ORF. These observations point to a novel form of microcompartmentalization and render the MOCS genes ideal candidates for a somatic gene therapy approach.
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PMID:Genetics of molybdenum cofactor deficiency. 1074 56

Cerebral hypoxia in the fetus and newborn results in neonatal morbidity and mortality as well as long-term sequelae such as mental retardation, seizure disorders, and cerebral palsy. In the developing brain, determinants of susceptibility to hypoxia should include the lipid composition of the brain cell membrane, the rate of lipid peroxidation, the presence of antioxidant defenses, and the development and modulation of excitatory amino acid neurotransmitter receptors such as the N-methyl-D-aspartate (NMDA) receptor, the intracellular Ca2+, and the intranuclear Ca(2+)-dependent mechanisms. In addition to the developmental status of these cellular components, the response of these potential mechanisms to hypoxia determines the fate of the hypoxic brain cell in the developing brain. Using electron spin resonance spectroscopy of alpha-phenyl-N-tert-butyl-nitrone spin adducts, studies from our laboratory demonstrated that tissue hypoxia results in increased free radical generation in the cortex of fetal guinea pigs and newborn piglets. Pretreatment with MgSO4 significantly decreased the hypoxia-induced increase in free radical generation in the term fetal brain. We also showed that brain tissue hypoxia modifies the NMDA receptor ion-channel recognition and modulatory sites. Furthermore, a higher increase in NMDA receptor agonist-dependent Ca2+ in synaptosomes was demonstrated. The increase in intracellular Ca2+ may activate several enzymatic pathways such as phospholipase A2 and metabolism of archidonic acid by cyclooxygenase and lipoxygenase, conversion of xanthine dehydrogenase to xanthine oxidase by proteases, and activation of nitric oxide synthase. Using inhibitors of each of these enzymes such as cyclooxygenase (indomethacin), lipoxygenase (nordihydroguaiaretic acid), xanthine oxidase (allopurinol), and nitric oxide synthase (N-nitro-L-arginine), studies have shown that these enzyme reactions result in oxygen free radical generation, membrane peroxidation, and cell membrane dysfunction in the hypoxic brain. Specifically, generation of nitric oxide free radicals during hypoxia may lead to nitration and nitrosylation of specific membrane proteins and receptors, resulting in dysfunction of receptors and enzymes. We conclude that hypoxia-induced modification of the NMDA receptor leading to increased intracellular Ca2+ results in free radical generation and cell injury. We suggest that during hypoxia the increased intracellular Ca2+ may lead to increased intranuclear Ca2+ concentration and alter nuclear events including transcription of specific apoptotic genes and activation of endonucleases, resulting in programmed cell death.
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PMID:Mechanisms of perinatal cerebral injury in fetus and newborn. 1081 2

Human molybdenum cofactor deficiency is a rare and devastating autosomal-recessive disease for which no therapy is known. The absence of active sulfite oxidase-a molybdenum cofactor-dependent enzyme-results in neonatal seizures and early childhood death. Most patients harbor mutations in the MOCS1 gene, whose murine homolog was disrupted by homologous recombination with a targeting vector. As in humans, heterozygous mice display no symptoms, but homozygous animals die between days 1 and 11 after birth. Biochemical analyis of these animals shows that molydopterin and active cofactor are undetectable. They do not possess any sulfite oxidase or xanthine dehydrogenase activity. No organ abnormalities were observed and the synaptic localization of inhibitory receptors, which was found to be disturbed in molybdenum cofactor deficient-mice with a Gephyrin mutation, appears normal. MOCS1(-/-) mice could be a suitable animal model for biochemical and/or genetic therapy approaches.
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PMID:Molybdenum cofactor-deficient mice resemble the phenotype of human patients. 1247 Oct 57

Molybdenum cofactor deficiency leads to combined deficiency of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase enzyme activities. The major clinic symptom is intractable seizures seen soon after birth. No definite therapy is available. We report here a newborn with molybdenum cofactor deficiency-associated Dandy-Walker malformation who presented with severe lactic acidosis and intracranial hemorrhage.
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PMID:Molybdenum cofactor deficiency presenting with severe metabolic acidosis and intracranial hemorrhage. 1579 86


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