The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform
Shigeo Kure - One of the best experts on this subject based on the ideXlab platform.
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Glycine cleavage system in neurogenic regions
2014Co-Authors: Prof Z. Molnar, Shigeo Kure, Kanako Kojima, Akiko Ichinohe, Sumiko Mikawa, Takatoshi Ueki, Kazuko Fujiwara, Kazuie Iinuma, Kohji SatoAbstract:Hyperglycinemia, rat, neural stem cell. Ichinohe A et al. 2 The glycine cleavage system (GCS) is the essential enzyme complex for degrading glycine and supplying 5,10-methylenetetrahydrofolate for DNA synthesis. Inherited deficiency of this system causes non-ketotic Hyperglycinemia, characterized by severe neurological symptoms and frequent association of brain malformations. Although high levels of glycine have been considered to cause the above-mentioned problems, the detailed pathogenesis of this disease is still unknown. Here we show that GCS is abundantly expressed in rat embryonic neural stem/progenitor cells in the neuroepithelium, and this expression is transmitted to the radial glia-astrocyte lineage, with prominence in postnatal neurogenic regions. These data indicate that GCS plays important roles in neurogenesis, and suggest that disturbance of neurogenesis induced by deficiency of GCS may be the main pathogenesis of non-ketotic Hyperglycinemia
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two novel laboratory tests facilitating diagnosis of glycine encephalopathy nonketotic Hyperglycinemia
Brain & Development, 2011Co-Authors: Shigeo KureAbstract:Glycine encephalopathy (GE), also known as non-ketotic Hyperglycinemia, is a life-threatening metabolic disease caused by inherited deficiency of the glycine cleavage system (GCS). GE is characterized by accumulation of a large amount of glycine in serum and cerebrospinal fluids. In typical cases with GE, coma, profound hypotonia, and intractable seizures develop within several days of life. Patients with atypical symptoms may have delayed or missed diagnosis because of non-specific symptoms. It is sometimes problematic to confirm the diagnosis of GE since it requires either invasive liver biopsy for measurement of GCS activity or exhaustive mutational screening of three GCS genes, GLDC, AMT, and GCSH. We herein describe two novel laboratory tests for diagnosis of GE, [1-(13)C]glycine breath test and the multiplex ligation-dependent probe amplification (MLPA) for detection of large deletions in GLDC. The [1-(13)C]glycine breath test has been developed for noninvasive enzymatic diagnosis of GE. Because the GCS generates CO(2) by degradation of glycine, the GCS activity could be evaluated in vivo by measurement of exhaled (13)CO(2) after administration of a stable isotope, [1-(13)C]glycine. The MLPA has been developed for improvement in mutation detection rate in GE: Deletions involving multiple GDLC exons are prevalent among GE patients, but cannot be detected by the exon-sequencing analysis. Two novel diagnosis methods would facilitate diagnosis of hyperglycinemic patients as having GE.
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Nonketotic Hyperglycinemia: proposal of a diagnostic and treatment strategy.
Pediatric neurology, 2010Co-Authors: Yuka Suzuki, Shigeo Kure, Masaaki Oota, Hitomi Hino, Mitsumasa FukudaAbstract:Early myoclonic encephalopathy presents neonatally with fragmented myoclonus and a suppression-burst electroencephalography pattern. We describe a newborn boy with early myoclonic encephalopathy caused by nonketotic Hyperglycinemia. He presented with severe hypotonia, progressive apneic episodes, and erratic myoclonus. Screening of deletions in GLDC, using the multiplex ligation-dependent probe amplification method, and a 13C breath test confirmed the diagnosis of nonketotic Hyperglycinemia. Treatment with the N-methyl-d-aspartate receptor antagonist ketamine exerted dramatic suppressive effects on his seizures, and ameliorated his clinical status.
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Mild variant of nonketotic Hyperglycinemia with typical neonatal presentations: mutational and in vitro expression analyses in two patients.
The Journal of pediatrics, 2004Co-Authors: Shigeo Kure, Kanako Kojima, Akiko Ichinohe, Kenichi Sato, Zenro Kizaki, Fumio Inoue, Chutaro Yamanaka, Yoichi MatsubaraAbstract:In neonatal-onset nonketotic Hyperglycinemia, severe psychomotor retardation is the expected uniform outcome. We report two patients with typical neonatal presentation who showed far better developmental outcomes. The in vitro expression analysis of the identified GLDC mutations revealed considerable residual enzyme activity, suggesting prognostic and enzymatic heterogeneity even in neonatal-onset nonketotic Hyperglycinemia.
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Heterozygous GLDC and GCSH gene mutations in transient neonatal Hyperglycinemia.
Annals of neurology, 2002Co-Authors: Shigeo Kure, Kanako Kojima, Akiko Ichinohe, Tomoki Maeda, Rozália Kálmánchey, György Fekete, Suzan Z. Berg, Jim Filiano, Yoko Aoki, Yoichi SuzukiAbstract:Transient neonatal Hyperglycinemia is clinically or biochemically indistinguishable from nonketotic Hyperglycinemia at onset. In the case of transient neonatal Hyperglycinemia, the elevated plasma and cerebrospinal fluid glycine levels are normalized within 2 to 8 weeks. To elucidate the pathogenesis of transient neonatal Hyperglycinemia, we studied three patients by screening mutations in the genes that encode three components of the glycine cleavage system. Heterozygous mutations were identified in all of the three patients, suggesting that transient neonatal Hyperglycinemia develops in some heterozygous carriers for nonketotic Hyperglycinemia.
Chesa G. Chauke - One of the best experts on this subject based on the ideXlab platform.
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the effect of hyperglycinemic treatment in captive bred vervet monkeys chlorocebus aethiops
Metabolic Brain Disease, 2019Co-Authors: Zandisiwe E. Magwebu, Mikateko Mazinu, Sahar Abdulrasool, Chesa G. ChaukeAbstract:Nonketotic Hyperglycinemia (NKH) is a neuro-metabolic disorder caused by a deficiency in the glycine cleavage system (GCS) and glycine transporter 1 (GlyT1). A case of atypical late onset of NKH has been reported in a colony of captive-bred Vervet monkeys. The purpose of this study was to evaluate the effect of sodium benzoate and dextromethorphan in reducing glycine levels in hyperglycinemic monkeys. Twelve captive-bred Vervet monkeys were assigned into three groups consisting of four animals (control, valproate induced and cataract with spontaneous Hyperglycinemia). Valproate was used to elevate glycine levels and the induced group was then treated with sodium benzoate and dextromethorphan together with group three to normalise glycine levels in cerebrospinal fluid (CSF) and plasma. Valproate induction elicited changes in phosphate, alkaline phosphatase and platelet count, however, no significant changes in the glycine levels were observed, and this might be due to the individual variability within the group. The treatment intervention was only obtained in the spontaneous group whereby the glycine levels were normalised in CSF and plasma. Therefore, it can be concluded that sodium benzoate and dextromethorphan treatment was effective and beneficial to the hyperglycinemic group.
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nonketotic Hyperglycinemia in captive bred vervet monkeys chlorocebus aethiops with cataracts
Journal of Medical Primatology, 2019Co-Authors: Sanele Khoza, Thobile Ngqaneka, Zandisiwe E. Magwebu, Chesa G. ChaukeAbstract:BACKGROUND Nonketotic Hyperglycinemia (NKH) is a rare metabolic disorder that is characterized by high levels of glycine in plasma and cerebrospinal fluid in humans. In this study, total congenital cataract captive-bred Vervet monkeys (Chlorocebus aethiops) that are hyperglycinemic were screened to identify mutations in Bola type 3 (BOLA3), glutaredoxin 5 (GLRX5), and lipoate synthase (LIAS) genes. METHODS Twenty-four Vervet monkeys (12 hyperglycinemic and 12 healthy controls) were selected for mutation analysis using polymerase chain reaction (PCR), Sanger sequencing, and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS Novel sequence variants were identified in BOLA3 (R23H and Q38R) and LIAS (R369I and A371A), and gene expression in the control group was significantly lower compared to the hyperglycinemic group (P < 0.05). CONCLUSION The data obtained from this study will contribute to generation of new knowledge regarding the involvement of these genes in NKH development.
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Nonketotic Hyperglycinemia in captive-bred Vervet monkeys (Chlorocebus aethiops) with cataracts.
Journal of medical primatology, 2019Co-Authors: Sanele Khoza, Thobile Ngqaneka, Zandisiwe E. Magwebu, Chesa G. ChaukeAbstract:BACKGROUND Nonketotic Hyperglycinemia (NKH) is a rare metabolic disorder that is characterized by high levels of glycine in plasma and cerebrospinal fluid in humans. In this study, total congenital cataract captive-bred Vervet monkeys (Chlorocebus aethiops) that are hyperglycinemic were screened to identify mutations in Bola type 3 (BOLA3), glutaredoxin 5 (GLRX5), and lipoate synthase (LIAS) genes. METHODS Twenty-four Vervet monkeys (12 hyperglycinemic and 12 healthy controls) were selected for mutation analysis using polymerase chain reaction (PCR), Sanger sequencing, and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS Novel sequence variants were identified in BOLA3 (R23H and Q38R) and LIAS (R369I and A371A), and gene expression in the control group was significantly lower compared to the hyperglycinemic group (P
Yoichi Suzuki - One of the best experts on this subject based on the ideXlab platform.
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Heterozygous GLDC and GCSH gene mutations in transient neonatal Hyperglycinemia.
Annals of neurology, 2002Co-Authors: Shigeo Kure, Kanako Kojima, Akiko Ichinohe, Tomoki Maeda, Rozália Kálmánchey, György Fekete, Suzan Z. Berg, Jim Filiano, Yoko Aoki, Yoichi SuzukiAbstract:Transient neonatal Hyperglycinemia is clinically or biochemically indistinguishable from nonketotic Hyperglycinemia at onset. In the case of transient neonatal Hyperglycinemia, the elevated plasma and cerebrospinal fluid glycine levels are normalized within 2 to 8 weeks. To elucidate the pathogenesis of transient neonatal Hyperglycinemia, we studied three patients by screening mutations in the genes that encode three components of the glycine cleavage system. Heterozygous mutations were identified in all of the three patients, suggesting that transient neonatal Hyperglycinemia develops in some heterozygous carriers for nonketotic Hyperglycinemia.
Zandisiwe E. Magwebu - One of the best experts on this subject based on the ideXlab platform.
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the effect of hyperglycinemic treatment in captive bred vervet monkeys chlorocebus aethiops
Metabolic Brain Disease, 2019Co-Authors: Zandisiwe E. Magwebu, Mikateko Mazinu, Sahar Abdulrasool, Chesa G. ChaukeAbstract:Nonketotic Hyperglycinemia (NKH) is a neuro-metabolic disorder caused by a deficiency in the glycine cleavage system (GCS) and glycine transporter 1 (GlyT1). A case of atypical late onset of NKH has been reported in a colony of captive-bred Vervet monkeys. The purpose of this study was to evaluate the effect of sodium benzoate and dextromethorphan in reducing glycine levels in hyperglycinemic monkeys. Twelve captive-bred Vervet monkeys were assigned into three groups consisting of four animals (control, valproate induced and cataract with spontaneous Hyperglycinemia). Valproate was used to elevate glycine levels and the induced group was then treated with sodium benzoate and dextromethorphan together with group three to normalise glycine levels in cerebrospinal fluid (CSF) and plasma. Valproate induction elicited changes in phosphate, alkaline phosphatase and platelet count, however, no significant changes in the glycine levels were observed, and this might be due to the individual variability within the group. The treatment intervention was only obtained in the spontaneous group whereby the glycine levels were normalised in CSF and plasma. Therefore, it can be concluded that sodium benzoate and dextromethorphan treatment was effective and beneficial to the hyperglycinemic group.
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nonketotic Hyperglycinemia in captive bred vervet monkeys chlorocebus aethiops with cataracts
Journal of Medical Primatology, 2019Co-Authors: Sanele Khoza, Thobile Ngqaneka, Zandisiwe E. Magwebu, Chesa G. ChaukeAbstract:BACKGROUND Nonketotic Hyperglycinemia (NKH) is a rare metabolic disorder that is characterized by high levels of glycine in plasma and cerebrospinal fluid in humans. In this study, total congenital cataract captive-bred Vervet monkeys (Chlorocebus aethiops) that are hyperglycinemic were screened to identify mutations in Bola type 3 (BOLA3), glutaredoxin 5 (GLRX5), and lipoate synthase (LIAS) genes. METHODS Twenty-four Vervet monkeys (12 hyperglycinemic and 12 healthy controls) were selected for mutation analysis using polymerase chain reaction (PCR), Sanger sequencing, and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS Novel sequence variants were identified in BOLA3 (R23H and Q38R) and LIAS (R369I and A371A), and gene expression in the control group was significantly lower compared to the hyperglycinemic group (P < 0.05). CONCLUSION The data obtained from this study will contribute to generation of new knowledge regarding the involvement of these genes in NKH development.
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Nonketotic Hyperglycinemia in captive-bred Vervet monkeys (Chlorocebus aethiops) with cataracts.
Journal of medical primatology, 2019Co-Authors: Sanele Khoza, Thobile Ngqaneka, Zandisiwe E. Magwebu, Chesa G. ChaukeAbstract:BACKGROUND Nonketotic Hyperglycinemia (NKH) is a rare metabolic disorder that is characterized by high levels of glycine in plasma and cerebrospinal fluid in humans. In this study, total congenital cataract captive-bred Vervet monkeys (Chlorocebus aethiops) that are hyperglycinemic were screened to identify mutations in Bola type 3 (BOLA3), glutaredoxin 5 (GLRX5), and lipoate synthase (LIAS) genes. METHODS Twenty-four Vervet monkeys (12 hyperglycinemic and 12 healthy controls) were selected for mutation analysis using polymerase chain reaction (PCR), Sanger sequencing, and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS Novel sequence variants were identified in BOLA3 (R23H and Q38R) and LIAS (R369I and A371A), and gene expression in the control group was significantly lower compared to the hyperglycinemic group (P
Gisella Terre'blanche - One of the best experts on this subject based on the ideXlab platform.
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Paracetamol prevents Hyperglycinemia in vervet monkeys treated with valproate
Metabolic brain disease, 2012Co-Authors: Jacques Viljoen, Jakobus J. Bergh, Lodewyk J. Mienie, Hercullas F. Kotze, Gisella Terre'blancheAbstract:Valproate administration increases the level of the inhibitory transmitter, glycine, in the urine and plasma of patients and experimental animals. Nonketotic Hyperglycinemia (NKH), an autosomal recessive disorder of glycine metabolism, causes increased glycine concentrations in blood, urine, and cerebrospinal fluid (CSF), most likely due to a defect in the glycine cleavage enzyme or possibly deficits in glycine transport across cell membranes. We investigated the relationship between the hyperglycinemic effect of valproate and induced pyroglutamic aciduria via paracetamol in the vervet monkey. Firstly it was determined if valproate could induce Hyperglycinemia in the monkey. The second aim was to increase glutamic acid (oxoproline) urine excretion using paracetamol as a pre-treatment and to assess whether valproate has an influence on the γ-glutamyl cycle. Hyperglycinemia was induced in healthy vervet monkeys when treated with a single oral dose of 50 mg/kg valproate. An acute dose of 50 mg/kg paracetamol increased oxoproline in the urine. Pre-treatment with paracetamol opposed the hyperglycinemic effect of valproate. However, the CSF:serum glycine ratio in a nonketotic monkey increased markedly after paracetamol treatment and remained high following valproate treatment. These results indicate that the γ-glutamyl cycle does indeed play a role in the hyperglycinemic effect of valproate treatment, and that paracetamol may have value in preventing and/or treating valproate-induced NKH.