Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycine content and enzyme activity of the glycine cleavage system were compared in autopsied brain from five infants dying with glycine encephalopathy and four control infants, including two with other types of hyperglycinemia. Glycine content was elevated 2- to 8-fold and glycine cleavage enzyme activity was undetectable in the brains of the glycine encephalopathy patients. Glycine content and enzyme activity were normal in the brains of the control patients, including one with ketotic hyperglycinemia secondary to methylmalonic acidemia. Prolonged dialysis failed to restore glycine cleavage enzyme activity in brain homogenates of glycine encephalopathy patients, and these homogenates failed to inhibit enzyme activity when added to homogenates of control brain. Radioactive bicarbonate was converted to radioactive glycine by control brain, but not by glycine encephalopathy brain. This finding, together with the results of recombination experiments between solubilized human brain enzymes and purified protein components of the bacterial glycine cleavage system of Arthrobacter globiformis, indicates that the enzyme defect in glycine encephalopathy involves at least the second or H protein of the 4-protein glycine cleavage enzyme system.
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PMID:Studies of the glycine cleavage enzyme system in brain from infants with glycine encephalopathy. 59 63

In hepatic coma as well as diabetic coma severe disturbances occur in the amino acid metabolism. The defect lies in completely different levels which result two different plasma aminograms (PAG). In 24 patients with hepatic encephalopathy stage III-IV (7 patients with acute and 17 with chronic liver failure) the PAG were evaluated. The determination of the plasma amino acids (PAA) was carried out on Multichrom B (Beckmann, Munich). In hepatic coma high concentrations of Met, Tyr, Ala, Lys and Arg are found. The deviations of PAA from normal controls show between acute and chronic hepatic failure no qualitative but only quantitative differences. In diabetic coma the three branches chain AA (Val, Leu and Ile) were elevated upon 3--5 times of normal. Near normal concentrations are found for the AA Thr, Ser, Gly, Ala, Met and the aromatic AA (Phe and Tyr). The quotient between the branched chain and aromatic AA lies for hepatic coma at a mean of 1.18 and by diabetic coma at 7.18 (p less than 0.001). In hepatic coma a correlation exists between the level of the AA-quotient improvement and the decrease with a deterioriation of the metabolic encephalopathy. The high level of the AA-quotient in the patients of diabetic "coma" gives therefore a good explanation for the rare unconscious state of these patients.
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PMID:[Differences in plasma aminograms in hepatic and diabetic coma]. 74 45

To classify the influence of neurotransmitters in the genesis of uremic encephalopathy we studied cerebrospinal fluid (CSF) and plasma (P) amino acid (AA) concentration, in patients undergoing various dialytic treatments (hemodialysis = HD, intermittent and continuous peritoneal dialysis = IPD and CAPD). HD causes a significant decrease in CSF/P ratios of branched chain AA (BCAA) and a significant increase in CSF Glycine/Valine ratio, suggesting an augmented brain uptake of Glycine at detriment of Valine. In IPD the general trend of Aromatic AA/BCAA ratio suggests a preferential transport of Aromatic AA through the blood brain barrier. The differences between IPD and HD are confirmed by data concerning metabolites of Serotonin and Dopamine: CSF concentrations of 5- Hydroxyindoleacetic acid and Homovanillic acid are low in HD but high in IPD. So, a reduced (in HD) and an increased (in IPD) activity of monoamine systems could be at the basis of some neurological disturbances appearing in uremia.
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PMID:The role of neurotransmitters in the genesis of uremic encephalopathy. 614 71

Three cases of ketotic hyperglycinemia are described. Spongy encephalopathy was present in white as well as gray matter. The cell type that predominantly exhibited swelling was the astrocyte. Glycine binding is required for activation of the NMDA receptor. By constant excitation a surplus of glycine could disturb the ion balance. This might provide the pathogenetic principle of seizures and cytotoxic edema in hyperglycinemia.
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PMID:Spongy encephalopathy in ketotic hyperglycinemia. 769 92

A patient with neonatal glycine encephalopathy who had severe neurologic retardation, spasticity, and seizures died at 17 years of age. Glycine concentration was markedly elevated in brain tissue, especially in the cerebellum. Neuropathologic study revealed spongy myelinopathy throughout the central nervous system and calcium oxalate crystals in the cerebellum, which are probably derived from degradation of glycine. Myelinopathy appeared to be static compared to neonatal patients. The neurologic manifestations of neonatal glycine encephalopathy are probably due to neurotransmitter abnormalities, not to myelin damage.
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PMID:Neonatal glycine encephalopathy: biochemical and neuropathologic findings. 849 44

We describe an A-to-G transition at nucleotide 10044 in the tRNA(Gly) gene of mitochondrial DNA in a sibship in which the proband died at age 8 years after a severe encephalopathy, a brother died of sudden and unexpected death, and the other six siblings had a combination of symptoms, including apparent life-threatening events and gastroesophageal reflux. This novel mutation was very abundant (> 90%) in liver and muscle of the proband and in several tissues, including blood, from his affected siblings (range 91-99%) but was less abundant in blood from the asymptomatic mother (88%) and maternal grandmother (85%). Our findings further enlarge the spectrum of clinical presentations associated with mitochondrial DNA mutations.
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PMID:Novel mutation in the mitochondrial DNA tRNA glycine gene associated with sudden unexpected death. 888 49

GLUT1 deficiency is caused by a defect in the facilitative glucose transporter GLUT1. Impaired glucose transport across brain tissue barriers is reflected by hypoglycorrhachia and results in an epileptic encephalopathy with developmental delay and motor disorders. Recently heterozygous mutations in the GLUT1 gene (1p35-31.3) have been reported in sporadic patients. Parents and siblings carried the GLUT1 wild-type, suggesting a de novo, autosomal dominant condition resulting from GLUT1 haploinsufficiency. We report a father and two children from separate marriages affected by GLUT1 deficiency and carrying a novel heterozygous missense mutation (G272A) in the GLUT1 gene. Mutations were identified by polymerase chain reaction and DNA sequencing and confirmed by restriction fragment digest. The predicted amino acid change (Gly91Asp) affects an Arg-X-Gly-Arg-Arg motif between helices 2 and 3 that represents a cytoplasmic anchor point and is highly conserved among transporters of the major facilitator superfamily down to yeast and bacteria. GLUT1 immunoreactivity was normal, but 3-O-methyl-D-glucose uptake into erythrocytes was significantly reduced, suggesting a quantitatively normal, but functionally impaired, GLUT1 protein at the cell membrane. This is the first report of autosomal dominant transmission of GLUT1 deficiency, confirming that this condition is the result of haploinsufficiency. The Gly-->Asp mutation within a highly conserved sequence highlights its importance for GLUT1 function. GLUT1 deficiency should be considered in patients with epilepsy, mental retardation and motor disorders. Our observations have bearing on the identification of this treatable disorder in pediatric and adult patients, will modify current biochemical protocols which use parental controls and will enable genetic counseling of affected families.
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PMID:Autosomal dominant transmission of GLUT1 deficiency. 1113 15

This article summarizes data and issues covered in the workshop on Glycine Encephalopathy using headings that cover important topics in our present knowledge of this disease.
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PMID:Glycine encephalopathy (nonketotic hyperglycinaemia) : review and update. 1527 69

Glycine encephalopathy (GE) (non-ketotic hyperglycinemia) is an autosomal recessive neurometabolic disease caused by defective activity of the glycine cleavage system. Clinically, patients present usually in the neonatal period with hypotonia, encephalopathy, hiccups and breath arrests with or without overt seizures. GE is considered rare, but its incidence is relatively high in several geographical areas around the world. We report a novel mutation causing GE in six extended Arab families, all from a small suburban village (population 5,000). A methionine to threonine change in the initiation codon of the glycine decarboxylase gene led to markedly reduced glycine decarboxylase mRNA levels and abolished glycine cleavage system activity.
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PMID:A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem. 1586 13

Glycine has important neurotransmitter functions at inhibitory and excitatory synapses in the vertebrate central nervous system. The effective synaptic concentrations of glycine are regulated by glycine transporters (GlyTs), which mediate its reuptake into nerve terminals and adjacent glial cells. GlyTs are members of the Na(+)/Cl(-)-dependent transporter family, whose activities and subcellular distributions are regulated by phosphorylation and interactions with other proteins. The analysis of GlyT knockout mice has revealed distinct functions of individual GlyT subtypes in synaptic transmission and provided animal models for two hereditary human diseases, glycine encephalopathy and hyperekplexia. Selective GlyT inhibitors could be of therapeutic value in cognitive disorders, schizophrenia and pain.
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PMID:Glycine transporters: essential regulators of neurotransmission. 1595 Aug 77


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