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)

A simple fluorescent spot screening test has been developed for the identification of individuals with arginase deficiency (hyperargininemia). The assay is based on the coversion of arginine to ornithine and urea by arginase present in 1/8 inch disc of dried blood on filter paper. The enzyme activity is visually estimated by the oxidation of NAD-H to NAD+ in a coupled kinetic reaction. In the absence of the enzyme, there is no oxidation of the NAD-H and consequently no loss of fluorescence. The screening assay has been used to identify successfully both heterozygous and homozygous arginase-deficient crabeater macaques (M. fascicularis) as well as three patients with hyperargininemia. This test can be used to screen large numbers of patients with mental retardation or seizure disorders rapidly to determine the frequency of this disorder more precisely.
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PMID:A simple screening test for arginase deficiency (hyperargininemia). 84 87

Congenital hyperargininaemia is a rare condition transmitted as an autosomal dominant trait. Following a one-year free interval, repeated vomiting, psychomotor regression and spastic paraparesis with talipes equinus progressively develop. The diagnosis, confirmed by arginine assays in blood and urine, is probably often missed. We report a case of homozygous arginase deficiency belatedly diagnosed at the age of 18 years, when treatment with sodium valproate (VPA) was instituted. This female patient presented with psychomotor regression since the age of 15 months and with paraparesis since she was 3 years' old. These symptoms rapidly became worse. At the age of 18 years, when she was bed-ridden, she was hospitalized for subintrant tonic seizures. EEG showed generalized, continuous spike-wave discharges at the rate of 3.5 c/s. Treatment with VPA was instituted. Five days later, she went into a state of stupor. Blood ammonia level was elevated at 362 mumol/l. VPA was discontinued, and this was followed by a regression of disturbances of consciousness and by a decrease in arterial ammoniaemia, although the ammonia levels remained high, fluctuating between 40 and 100 mumol/l. Several months after VPA treatment was interrupted, the patient had a second episode of stupor, and her ammoniaemia was 500 mumol/l. Serum amino acid chromatography showed hyperargininaemia at 501 mumol/l (N = 30-150 mumol/l). The diagnosis of arginase deficiency was confirmed by the rise of arginine in red cells, cerebrospinal fluid and urine and, above all, by the finding of a deeply depressed arginase activity in erythrocytes. In all cases of intolerance to VPA, arterial ammoniaemia should be measured after withdrawal of VPA, some time after the acute episode.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Late diagnosis of congenital argininemia during administration of sodium valproate]. 229 Oct 40

Low blood manganese (Mn2+) concentration is associated with epilepsy in humans and rats. The low Mn2+ concentration is attributed by some investigators to the seizure activity associated with the epilepsy, whereas others propose that the low Mn2+ concentration may be secondary to genetic mechanisms underlying the epilepsy. To begin to differentiate between these possibilities, Mn(2+)-binding enzymes of liver and brain (i.e., arginase and glutamine synthetase, respectively) were assayed in rats exposed to chronically induced seizures and in genetically epilepsy-prone rats (GEPRs). Chronic seizures caused a decrease in whole blood Mn2+ levels but did not affect brain Mn2+ concentrations. Arginase activity was increased in livers of rats with chronic seizure as compared with controls, but this difference was eliminated when Mn2+ was added to the assay. Brain glutamine synthetase activity was unaffected by chronic seizures, but the activity of this enzyme was significantly lower in GEPR brain than in control brain. Liver arginase activity tended to be lower in GEPRs, although the difference was not statistically significant. These data indicate that seizures affect liver arginase activity through changes in liver Mn2+ concentration, but GEPRs show abnormalities in Mn(2+)-dependent enzymes apparently independent of seizure activity.
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PMID:Manganese and epilepsy: brain glutamine synthetase and liver arginase activities in genetically epilepsy prone and chronically seizured rats. 809 25

Arginase deficiency is a rare, autosomal recessive, disorder of the urea cycle characterized by mild hyperammonaemia, hyperargininaemia, dibasic aminoaciduria and orotic aciduria, associated with progressive spastic tetraplegia, seizures, psychomotor retardation, and growth failure. We report a family who presented with their daughter at 4 years 11 months of age with an acute encephalopathy. Initial laboratory results revealed hyperammonaemia (160 micromol/L; normal 0-34), hyperargininaemia (512 micromol/L; normal 23-86) and orotic aciduria. A diagnosis of arginase deficiency was confirmed by enzyme assay, and treatment with a modified protein-restricted diet along with sodium benzoate therapy was initiated. Over time, intellectual development has been normal, but the child developed spasticity in her lower extremities. Subsequently, the mother presented at 6 weeks of pregnancy seeking prenatal diagnosis. Prenatal testing for arginase deficiency has only been reported in one other case. Arginase is not expressed in cultured amniotic fluid cells or chorionic villus samples. Testing for arginase activity assay in red blood cells, isolated by cordocentesis, was performed and predicted an unaffected fetus. The result was confirmed by postnatal enzyme analysis of red cells from the newborn. On the basis of our experience, prenatal diagnosis of arginase deficiency by cord red blood cell arginase activity assay appears possible.
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PMID:Prenatal diagnosis for arginase deficiency: a case study. 1460 7

No comparative studies have addressed the oxidant and antioxidant states of blood and cerebrospinal fluid. To reveal this differential state, the study was designed to identify the seizure type with the worse prognosis by determining erythrocyte arginase and erythrocyte catalase, plasma and cerebrospinal fluid malondialdehyde, and plasma and cerebrospinal fluid nitric oxide levels. Study groups were classified as febrile (group 1, n = 21), afebrile (group 2, n = 21), and control (group 3, n = 41, subdivided as 3a, febris positive, convulsion negative, and 3b, febris negative, convulsion negative). Levels of erythrocyte arginase, erythrocyte catalase, plasma malondialdehyde, cerebrospinal fluid malondialdehyde, plasma nitric oxide, and cerebrospinal fluid nitric oxide levels were determined for all groups. A difference was detected between the control and febrile seizure groups with respect to erythrocyte catalase and plasma and cerebrospinal fluid levels of nitric oxide (P < 0.05). Both febrile states and convulsions influence oxidative mechanism. Oxidative stress-generating potential differs for febrile and afebrile seizures. In afebrile seizures, greater levels of oxidative stress might affect prognosis adversely. This phenomenon can be interpreted in terms of fever as a protective factor against possible neurological damage during convulsive seizures.
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PMID:Effects of febrile and afebrile seizures on oxidant state in children. 1750 62

Nitric oxide (NO), a potential candidate for a modulator of convulsive activity, is a mediator in several pathological events in the central nervous system. The polyamines, spermidine (Spd) and spermine, are neuromodulators influencing the metabolism of L-arginine and NO production. Here we examined the effects of Spd on NO production and arginase activity during convulsions induced by pentylenetetrazol (PTZ). Male Wistar rats were allocated into four experimental groups of 8 animals each and received the following treatments: I (control)--saline, intraperitoneally (i.p.); II (PTZ)--seizures induced by pentylenetetrazol (100mg/kg bw i.p); III (Spd)--Spd (1 mg/kg bw i.p.) 50 min before PTZ application; IV (Mid)--antiepileptic Midazolam (100 mg/kg bw) 45 min before PTZ. In brain cortex, striatum, hippocampus, cerebellum, and brainstem homogenates, nitrite + nitrate levels and arginase activity were determined. Spermidine showed proepileptic effects. shortening seizure latency and inducing a more profound increase of NO production than PTZ in all brain structures. PTZ reduced arginase activity, whereas Spd pretreatment increased enzyme activity, with the most profound effects in cerebellum and brainstem. The results point out the importance of polyamine and arginine metabolism in the brain during seizures, suggesting a regulatory role for polyamines and arginase in NO production.
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PMID:Spermidine influence on the nitric oxide synthase and arginase activity relationship during experimentally induced seizures. 2085 99

Enzyme defects of the urea cycle typically present with significant hyperammonemia and its associated toxicity, in the first few months of life. However, arginase I (ARG1) deficiency, a rare autosomal recessive disorder, has classically been the exception. ARG1 deficiency usually presents later in life with spasticity, seizures, failure to thrive and developmental regression. Neonatal and early infantile presentation of ARG1 deficiency with severe hyperammonemia remains rare and only six such cases have been described. We report a severely affected infant with ARG1 deficiency who presented at 6 weeks of age with lethargy, poor feeding and severe encephalopathy caused by hyperammonemia. The clinical and biochemical features of the proband and six other previously reported cases with neonatal or infantile-onset presentation of ARG1 deficiency with hyperammonemia are reviewed. In addition, the clinical spectrum of seven previously unpublished patients with later onset ARG1 deficiency, who also experienced recurrent hyperammonemia, is presented. Several biochemical abnormalities have been postulated to play a role in the pathogenesis of the neurological changes in ARG1 deficiency including hyperargininemia, elevated guanidino compounds and elevated glutamine levels, as well as the hyperammonemia. The index case demonstrated many of these. The cases reviewed here suggest a genotype/phenotype correlation and advocate for the addition of arginine as a primary target in newborn screening programs.
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PMID:Arginase I deficiency: severe infantile presentation with hyperammonemia: more common than reported? 2180 29

Hyperargininemia is an autosomal recessive metabolic disorder caused by a deficiency of enzyme arginase I. It is a rare pan-ethnic disease with a clinical presentation distinct from that of other urea cycle disorders, and hyperammonemic encephalopathy is not usually observed. Hyperargininemia is one of the few treatable causes of pediatric spastic paraparesis, and can be confused with cerebral palsy. We retrospectively evaluated the clinical onset, neurologic manifestations, progression of abnormalities, electroencephalographic abnormalities, and laboratory findings of 16 Brazilian patients with hyperargininemia. Relevant data about the clinical spectrum and natural history of hyperargininemia are detailed. Progressive spastic diplegia constituted the key clinical abnormality in this group, but variability in clinical presentation and progression were evident in our series. Seizures in hyperargininemia may be more common than reported in previous studies. Features distinguishing hyperargininemia from cerebral palsy and hereditary spastic paraplegia are emphasized in this large series of patients.
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PMID:Clinical features and neurologic progression of hyperargininemia. 2263 32

Arginase deficiency is characterized by hyperargininemia and infrequent episodes of hyperammonemia. Human patients suffer from neurological impairment with spasticity, loss of ambulation, seizures, and severe mental and growth retardation. In a murine model, onset of the phenotypic abnormality is heralded by weight loss beginning around day 15 with death occurring typically by postnatal day 17 with hyperargininemia and markedly elevated ammonia. The goal of this study was to address the development of a gene therapy approach for arginase deficiency beginning in the neonatal period. Lifespan extension, body weight, circulating amino acids and ammonia levels were examined as outcome parameters after gene therapy with an adeno-associated viral vector expressing arginase was administered to mice on the second day of life (DOL). One-hundred percent of untreated arginase-deficient mice died by DOL 24, whereas 89% of the adeno-associated virus (AAV)-treated arginase deficient mice have survived for >8 months. While animals at 8 months demonstrate elevated glutamine levels, ammonia is less than three times that of controls and arginine levels are normal. These studies are the first to demonstrate that AAV-based therapy for arginase deficiency is effective and supports the development of gene therapy for this and the other urea cycle disorders.
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PMID:Long-term survival of the juvenile lethal arginase-deficient mouse with AAV gene therapy. 2276 May 43

Complete arginase I deficiency is the least severe urea cycle disorder, characterized by hyperargininemia and infrequent episodes of hyperammonemia. Patients suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation and seizures, and is associated with intellectual disability. In mice, onset is heralded by weight loss beginning around day 15; gait instability follows progressing to inability to stand and development of tail tremor with seizure-like activity and death. Here we report that hyperargininemic mice treated neonatally with an adeno-associated virus (AAV)-expressing arginase and followed long-term lack any presentation consistent with brain dysfunction. Behavioral and histopathological evaluation demonstrated that treated mice are indistinguishable from littermates, and that putative compounds associated with neurotoxicity are diminished. In addition, treatment results in near complete resolution of metabolic abnormalities early in life; however, there is the development of some derangement later with decline in transgene expression. Ammonium challenging revealed that treated mice are affected by exogenous loading much greater than littermates. These results demonstrate that AAV-based therapy for hyperargininemia is effective and prevents development of neurological abnormalities and cognitive dysfunction in a mouse model of hyperargininemia; however, nitrogen challenging reveals that these mice remain impaired in the handling of waste nitrogen.
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PMID:AAV-based gene therapy prevents neuropathology and results in normal cognitive development in the hyperargininemic mouse. 2338 1


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