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

Homocystinuria with elevated plasma homocysteine and methionine levels is the result of deficient activity of cystathionine synthetase, the enzyme catalyzing conversion of homocysteine to cystathionine. It is inherited as an autosomal recessive trait with a worldwide distribution. The major clinical manifestations result from the elevated plasma homocysteine level. The excitotoxic effect of homocysteic acid accounts for mental retardation and seizures. Interference with collagen cross-linking by sulfhydryl groups of homocysteine causes ectopia lentis and skeletal deformities. Sulfation factor-like effects contribute to disruption of vascular endothelium, which is followed by platelet thrombosis and widespread arterial and venous occlusions. Low methionine homocystinuria, with deficient remethylation of homocysteine, results from deranged vitamin B(12) metabolism and from deficient 5,10-methylene-tetrahydrofolate reductase. Administration of azaribine produces homocystinuria by mechanism not yet elucidated.
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PMID:Homocystinuria: pathogenetic mechanisms. 32 77

Two infants of homocystinuria with a defective activity of the N5,10-methylenetetrahydrofolate reductase in the liver, kidney, brain and/or leukocytes were reported. Contrary to four cases with similar biochemical defects reported up to date, the two cases of ours demonstrated peculiar clinical features characterized by an early onset in infancy, fits of apnea and seizures, downhill course with coma, and death within one year of life. Thus "an infantile type" of this disorder was advanced as a new clinical entity. Assay for the N5,10-methylenetetrahydrofolate reductase activity using peripheral leukocytes was established and might be useful for a diagnosis of this disorder and also for detection of heterozygotes.
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PMID:Infantile type of homocystinuria with N5,10-methylenetetrahydrofolate reductase defect. 84 45

Two male term babies were born at Mackay Memorial Hospital; both were born without incident. Newborn screenings (including phenylketonuria, homocystinuria, galactosemia, congenital hypothyroidism and G-6-PD deficiency) were performed at the age of three days and judged to be normal. In the later neonatal period, case 1 gradually developed prolonged jaundice, poor feeding and poor weight gain. The rechecked thyroid stimulating hormone (TSH) level was 276.3 mU/l. Case 2 was admitted with seizures; the TSH level, rechecked by chance, showing 11.6 mU/l. Under the suspicion of congenital hypothyroidism, serum confirmation tests were performed and showed TSH 393.6 mU/l, 37.09 mU/l and T4 2.87 micrograms/dl, 4.59 micrograms/dl, respectively. The diagnosis was, thus, congenital hypothyroidism with delayed rise in TSH level. The conclusion is that, regardless of the result of newborn screening, a serum confirmation test (T4 & TSH level) should be done in any infant who is suspected to have congenital hypothyroidism.
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PMID:[Congenital hypothyroidism missed on newborn screening: report of two cases]. 226 Apr 71

Homocystinuria is an inborn error of methionine metabolism, of which cause is mainly deficiency of cystathionine synthetase. The major clinical manifestations of homocystinuria are mental retardation, seizures, ectopia lentis, skeletal deformities and occlusive vascular disease. A case of homocystinuria accompanied with deep cerebral venous thrombosis was reported. A 29-year-old woman was admitted to our hospital with unconsciousness and tetraparesis on December 7, 1984. She was diagnosed as homocystinuria due to cystathionine synthetase deficiency at 13-year-old. Amino acid analysis of serum revealed homocystinaemia (1.37 mg/dl, normal 0), hypermethioninaemia (1.27 mg/dl, normal 0.2-0.48) and low cystathionine content. CT scan revealed intraventricular hemorrhage and diffuse low density in basal ganglia and white matter. Cerebral angiograms showed that deep cerebral veins and superior sagittal sinus can not be recognized clearly in any phase, and Sylvian veins are opacified markedly. It is suggested that intraventricular hemorrhage, and low density area in basal ganglia and white matter is due to hemorrhagic infarction by venous thrombosis of internal cerebral vein. The major clinical manifestations of homocystinuria result from the elevated plasma homocysteine level. The excitotoxic effect of homocysteic acid accounts for mental retardation and seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Homocystinuria accompanied with cerebral deep venous thrombosis--a case report]. 236 35

Functional methionine synthase deficiency is generally characterized by homocystinuria and hypomethioninemia in the absence of methylmalonic aciduria. Patients are divided into two classes, cblE and cblG, on the basis of complementation analysis. Presentation has usually been in the first 2 years of life, but one patient came to medical attention at age 21 years with symptoms initially diagnosed as multiple sclerosis. Common findings among 11 patients (4 with cblE and 7 with cblG) have included megaloblastic anemia (all patients) and various neurological deficits including developmental retardation (10 patients), cerebral atrophy (8 patients), hypotonia (7 patients), EEG abnormalities (6 patients), and nystagmus (5 patients). Hypertonia, seizures, blindness, and ataxia were less frequent. All patients have responded to therapy with cobalamin with resolution of anemia and biochemical abnormalities; neurological deficits resolved more slowly and in some cases incompletely. Hydroxycobalamin has been more effective than cyanocobalamin. Fibroblasts from patients with cblE (5 patients) and cblG (6 patients) all showed decreased intracellular levels of methylcobalamin (MeCbl) and decreased incorporation of label from 5-methyltetrahydrofolate into macromolecules, suggesting decreased activity of the MeCbl-dependent enzyme methionine synthase. Methionine synthase specific activity in extracts of all cblE fibroblasts was normal or near-normal under standard reducing conditions; synthase specific activity in extracts of 5 cblG patients was low but was high in a 6th patient measured in another laboratory. Thus, there is heterogeneity among patients with functional methionine synthase deficiency both in clinical presentation and in the results of biochemical studies of cultured cells.
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PMID:Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity. 268 21

Homocystinuria commonly affects the central nervous system (CNS), primarily as mental retardation, seizures, and stroke. Case reports have long suggested a predisposition to schizophrenia, but no careful study of predisposition to psychiatric illness has been performed. Accordingly, we evaluated 63 persons with homocystinuria due to cystathionine beta-synthase deficiency for psychiatric disturbance, intelligence, evidence of other CNS problems, and responsiveness to vitamin B6. The overall rate of clinically significant psychiatric disorders was 51%, predominated by four diagnostic categories: episodic depression (10%), chronic disorders of behavior (17%), chronic obsessive-compulsive disorder (5%), and personality disorders (19%). The average IQ was 80 +/- 27 (1 SD); and an IQ of less than or equal to 79 was two-thirds more common among vitamin B6-nonresponsive patients compared to vitamin B6-responsive patients. Aggressive behavior and other disorders of conduct were particularly common among patients with mental retardation and among vitamin B6-nonresponsive patients.
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PMID:Psychiatric manifestations of homocystinuria due to cystathionine beta-synthase deficiency: prevalence, natural history, and relationship to neurologic impairment and vitamin B6-responsiveness. 359 41

The effect of L-homocysteine and selected derivatives on the high-affinity uptake of the inhibitory neuroeffectors, GABA and taurine, was investigated in synaptosomes, and in cultured neurons and astrocytes. High-affinity uptake of taurine into synaptosomes was inhibited most effectively by L-homocysteine, DL-homocysteine and homocystine whereas neuronal uptake was unaffected by any of the compounds tested. The high affinity uptake of taurine into astrocytes was markedly inhibited by L-homocysteine, L-homocysteic acid and L-homocystine. High-affinity GABA uptake into astrocytes was notably inhibited by L-homocystine, none of the other compounds tested causing appreciable inhibition below a concentration of 5 mM. Neuronal and synaptosomal high-affinity uptake of GABA was not significantly affected by any of the test compounds at concentrations below 5 mM. The implication of these results to the study of the mechanism of homocysteine-induced seizures and their relevance to the genetic disorder homocystinuria is discussed.
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PMID:Effect of L-homocysteine and derivatives on the high-affinity uptake of taurine and GABA into synaptosomes and cultured neurons and astrocytes. 368 29

We present findings on an infant with neonatal megaloblastic anemia, homocystinuria, and neurologic dysfunction that included developmental delay and tonic seizures. There was no methylmalonic aciduria. Cyanocobalamin therapy was accompanied by complete hematologic and neurologic recovery, diminished homocystine excretion, and subsequently normal neurologic development. Cultured fibroblasts and lymphoblasts showed a reduced methionine synthase activity and a growth requirement for methionine. Cobalamin incorporation by the patient's lymphoblasts was normal, but the proportion of cellular methylcobalamin in the patient's lymphoblasts and fibroblasts were markedly reduced and that of adenosylcobalamin normal. The reduced methionine synthase activity was independent of assay reducing (thiol) conditions, but normal levels of activity accompanied culture of the patient's lymphoblasts in medium with markedly increased cobalamin concentration. The characteristics of the reduced methionine synthase of our patient differ significantly from that of the previously described infant with cobalamin E disease and suggest that genetic heterogeneity may characterize this mutation.
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PMID:Vitamin B12-responsive neonatal megaloblastic anemia and homocystinuria with associated reduced methionine synthase activity. 382 32

An international questionnaire survey has been conducted to define better the natural history of homocystinuria due to cystathionine beta-synthase deficiency and permit evaluation of treatment. Data were compiled for 629 patients. Among patients not discovered by newborn screening, B6-responsive individuals on the average have significantly better mental capabilities (mean IQ, 79) than do B6-nonresponsive individuals (mean IQ, 57). Time-to-event curves are presented for the other major clinical abnormalities produced by this disease. Each occurred at significantly lower rates in untreated B6-responsive than in untreated B6-nonresponsive patients, as shown by the following examples: (1) dislocation of optic lenses (at age 10, chances of dislocation: 55% and 82%, respectively); (2) initial clinically detected thromboembolic events (at age 15, chances of having had such an event: 12% and 27%, respectively); (3) radiologic detection of spinal osteoporosis (at age 15, chances of such osteoporosis having been detected: 36% and 64%, respectively); and (4) mortality (at age 30, chances of not surviving: 4% and 23%, respectively). Methionine restriction initiated neonatally prevented mental retardation, retarded the rate of lens dislocation, and may have reduced the incidence of seizures. Pyridoxine treatment of late-detected B6-responsive patients retarded the rate of occurrence of initial thromboembolic events. Following 586 surgical procedures, 25 postoperative thromboembolic complications occurred, six of which were fatal. Reproductive histories were reported predominantly for B6-responsive patients. Living offspring of either men or women patients had few abnormalities. The evidence is inconclusive whether untreated maternal cystathionine beta-synthase deficiency leads to excessive fetal loss. Only 13% of patients detected in screening programs of newborns and classified as to B6-responsiveness were B6-responsive, compared to 47% among late-detected patients. Current screening programs that identify neonatal hypermethioninemia may be preferentially failing to detect B6-responsive patients.
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PMID:The natural history of homocystinuria due to cystathionine beta-synthase deficiency. 387 65

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


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