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Keiko Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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SLC25A13 Gene Analysis in Citrin Deficiency: Sixteen Novel Mutations in East Asian Patients, and the Mutation Distribution in a Large Pediatric Cohort in China
2016Co-Authors: Sumito Dateki, Keiko Kobayashi, Lock-hock Ngu, Takeyori SahekiAbstract:Background: The human SLC25A13 gene encodes citrin, the liver-Type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenoTypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet. Methods and Results: By means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBan
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Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among thai infants
BMC gastroenterology, 2012Co-Authors: Suporn Treepongkaruna, Keiko Kobayashi, Suttiruk Jitraruch, Porawee Kodcharin, Dussadee Charoenpipop, Pim Suwannarat, Paneeya Pienvichit, Duangrurdee WattanasirichaigoonAbstract:Background The most common causes of cholestatic jaundice are biliary atresia and idiopathic neonatal hepatitis (INH). Specific disorders underlying INH, such as various infectious and metabolic causes, including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) especially, in East Asian populations are increasingly being identified. Since most NICCD infants recovered from liver disease by 1 year of age, they often are misdiagnosed with INH, leading to difficulty in determining the true prevalence of NICCD. Mutation(s) of human SLC25A13 gene encoding a mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), can lead to AGC2 deficiency, resulting in NICCD and an adult-onset fatal disease namely Citrullinemia Type II (CTLN2). To study the prevalence of NICCD and SLC25A13 mutations in Thai infants, and to compare manifestations of NICCD and non-NICCD, infants with idiopathic cholestatic jaundice or INH were enrolled. Clinical and biochemical data were reviewed. Urine organic acid and plasma amino acids profiles were analyzed. PCR-sequencing of all 18 exons of SLC25A13 and gap PCR for the mutations IVS16ins3kb and Ex16+74_IVS17-32del516 were performed. mRNA were analyzed in selected cases with possible splicing error.
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Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13mutations among thai infants
BMC Gastroenterology, 2012Co-Authors: Suporn Treepongkaruna, Keiko Kobayashi, Suttiruk Jitraruch, Porawee Kodcharin, Dussadee Charoenpipop, Pim Suwannarat, Paneeya Pienvichit, Duangrurdee WattanasirichaigoonAbstract:Background The most common causes of cholestatic jaundice are biliary atresia and idiopathic neonatal hepatitis (INH). Specific disorders underlying INH, such as various infectious and metabolic causes, including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) especially, in East Asian populations are increasingly being identified. Since most NICCD infants recovered from liver disease by 1 year of age, they often are misdiagnosed with INH, leading to difficulty in determining the true prevalence of NICCD. Mutation(s) of human SLC25A13 gene encoding a mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), can lead to AGC2 deficiency, resulting in NICCD and an adult-onset fatal disease namely Citrullinemia Type II (CTLN2). To study the prevalence of NICCD and SLC25A13 mutations in Thai infants, and to compare manifestations of NICCD and non-NICCD, infants with idiopathic cholestatic jaundice or INH were enrolled. Clinical and biochemical data were reviewed. Urine organic acid and plasma amino acids profiles were analyzed. PCR-sequencing of all 18 exons of SLC25A13 and gap PCR for the mutations IVS16ins3kb and Ex16+74_IVS17-32del516 were performed. mRNA were analyzed in selected cases with possible splicing error. Results Five out of 39 (12.8%) unrelated infants enrolled in the study were found to have NICCD, of which three had homozygous 851del4 (GTATdel) and two compound heterozygous 851del4/IVS16ins3kb and 851del4/1638ins23, respectively. Two missense mutations (p.M1? and p.R605Q) of unknown functional significance were identified. At the initial presentation, NICCD patients had higher levels of alkaline phosphatase (ALP) and alpha-fetoprotein (AFP) and lower level of alanine aminotransferase (ALT) than those in non-NICCD patients ( p < 0.05). NICCD patients showed higher citrulline level and threonine/serine ratio than non-NICCD infants ( p < 0.05). Fatty liver was found in 2 NICCD patients. Jaundice resolved in all NICCD and in 87.5% of non-NICCD infants at the median age of 9.5 and 4.0 months, respectively. Conclusion NICCD should be considered in infants with idiopathic cholestasis. The preliminary estimated prevalence of NICCD was calculated to be 1/48,228 with carrier rate of 1/110 among Thai infants. However, this number may be underestimated and required further analysis with mutation screening in larger control population to establish the true prevalence of NICCD and AGC2 deficiency.
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Failure to thrive and dyslipidemia caused by citrin deficiency: a novel clinical phenoType
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 2009Co-Authors: Yuan-zong Song, Keiko Kobayashi, Yanling Yang, Li Guo, Lian-shu Han, Takeyori SahekiAbstract:Two clinical phenoTypes for citrin deficiency (CD) have been reported. One is adult-onset Citrullinemia Type II (CTLN2) and another is neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). A child with CD and who had failure to thrive (FTT) and dyslipidemia as main clinical manifestations is reported here. Both the weight-and length-for-age at 18 months dropped below the 3rd percentile in the corresponding WHO anthropometry percentile charts, while blood biochemical analysis revealed dramatically increased triglyceride and total cholesterol, together with reduced HDL-cholesterol. Inquiries revealed his aversion to rice and fondness for fish since the age of one year, a peculiar habit which could not be corrected. Since the age of two years, the peculiar diet became more obvious, and slightly increased citrulline and threonine levels were detected on blood amino acid analysis. At the age of two years and five months he was suspected to have CD. Since then, he has been fed in accordance with his own food preferences, and FTT improved gradually, with weight-for-age, in particular, recovering beyond the 3rd percentile at three years of age, and dyslipidemia was also ameliorated gradually. SLC25A13 gene analysis revealed a homozygote of 851del4, and CD was thus confirmed. Diet survey at four years and seven months revealed a fondness for high-protein and low-carbohydrate foods, such as seafood, meat, eggs and milk. This child presented with FTT and dyslipidemia as main clinical manifestations and this was a novel CD phenoType different from NICCD and CTLN2.
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Citrullinemia Type II in a 64-year-old man with fluctuating serum citrulline levels: mutations in the SLC25A13 gene.
Journal of the neurological sciences, 2001Co-Authors: Hirofumi Maruyama, Masafumi Ogawa, Takeshi Nishio, Keiko Kobayashi, Takeyori Saheki, Nobuhiko SunoharaAbstract:Ž . Citrullinemia Type II CTLN2; OMIM 603471 is caused by the abnormality of the SLC25A13 gene, which encodes a calcium-binding mitochondrial carrier protein, designated w x citrin 1 . We reported a 64-year-old man with CTLN2 whose serum citrulline levels fluctuated between normal and abnormally high during episodic manifesting periods w x 2 . After publication, we obtained informed consent from the patient’s family to perform genetic diagnosis. DNA analysis of the SLC25A13 gene showed that the patient was a compound heterozygote for two known mutations, w x IVS11q1 G)A and IVS13q1 G)A 1 . Such a comw x bination is relatively rare 3 . The mutations, located at the 5 end of each intron, cause abnormal splicing and deletion Ž . of each exon 11 and 13 and result in the destruction of the mitochondrial transmembrane spanning structures of w x citrin 1,3 . It remains to be determined whether the clinical characteristics and prognosis of CTLN2 differ according to the Type of mutation. Though the prognosis is poor, liver transplantation at an early stage of the disease may prevent brain involvement. CTLN2 is a different disease from classical Citrullinemia Ž . CTLN1; OMIM 215700 caused by a deficiency of a different gene, argininosuccinate synthetase. Some CTLN2 patients might be misdiagnosed as having epilepsy or schizophrenia. Therefore, we emphasize the importance of making a definitive diagnosis at an early stage of the disease by analyzing the SLC25A13 gene.
Takeyori Saheki - One of the best experts on this subject based on the ideXlab platform.
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SLC25A13 Gene Analysis in Citrin Deficiency: Sixteen Novel Mutations in East Asian Patients, and the Mutation Distribution in a Large Pediatric Cohort in China
2016Co-Authors: Sumito Dateki, Keiko Kobayashi, Lock-hock Ngu, Takeyori SahekiAbstract:Background: The human SLC25A13 gene encodes citrin, the liver-Type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenoTypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet. Methods and Results: By means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBan
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Failure to thrive and dyslipidemia caused by citrin deficiency: a novel clinical phenoType
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 2009Co-Authors: Yuan-zong Song, Keiko Kobayashi, Yanling Yang, Li Guo, Lian-shu Han, Takeyori SahekiAbstract:Two clinical phenoTypes for citrin deficiency (CD) have been reported. One is adult-onset Citrullinemia Type II (CTLN2) and another is neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). A child with CD and who had failure to thrive (FTT) and dyslipidemia as main clinical manifestations is reported here. Both the weight-and length-for-age at 18 months dropped below the 3rd percentile in the corresponding WHO anthropometry percentile charts, while blood biochemical analysis revealed dramatically increased triglyceride and total cholesterol, together with reduced HDL-cholesterol. Inquiries revealed his aversion to rice and fondness for fish since the age of one year, a peculiar habit which could not be corrected. Since the age of two years, the peculiar diet became more obvious, and slightly increased citrulline and threonine levels were detected on blood amino acid analysis. At the age of two years and five months he was suspected to have CD. Since then, he has been fed in accordance with his own food preferences, and FTT improved gradually, with weight-for-age, in particular, recovering beyond the 3rd percentile at three years of age, and dyslipidemia was also ameliorated gradually. SLC25A13 gene analysis revealed a homozygote of 851del4, and CD was thus confirmed. Diet survey at four years and seven months revealed a fondness for high-protein and low-carbohydrate foods, such as seafood, meat, eggs and milk. This child presented with FTT and dyslipidemia as main clinical manifestations and this was a novel CD phenoType different from NICCD and CTLN2.
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Citrullinemia Type II in a 64-year-old man with fluctuating serum citrulline levels: mutations in the SLC25A13 gene.
Journal of the neurological sciences, 2001Co-Authors: Hirofumi Maruyama, Masafumi Ogawa, Takeshi Nishio, Keiko Kobayashi, Takeyori Saheki, Nobuhiko SunoharaAbstract:Ž . Citrullinemia Type II CTLN2; OMIM 603471 is caused by the abnormality of the SLC25A13 gene, which encodes a calcium-binding mitochondrial carrier protein, designated w x citrin 1 . We reported a 64-year-old man with CTLN2 whose serum citrulline levels fluctuated between normal and abnormally high during episodic manifesting periods w x 2 . After publication, we obtained informed consent from the patient’s family to perform genetic diagnosis. DNA analysis of the SLC25A13 gene showed that the patient was a compound heterozygote for two known mutations, w x IVS11q1 G)A and IVS13q1 G)A 1 . Such a comw x bination is relatively rare 3 . The mutations, located at the 5 end of each intron, cause abnormal splicing and deletion Ž . of each exon 11 and 13 and result in the destruction of the mitochondrial transmembrane spanning structures of w x citrin 1,3 . It remains to be determined whether the clinical characteristics and prognosis of CTLN2 differ according to the Type of mutation. Though the prognosis is poor, liver transplantation at an early stage of the disease may prevent brain involvement. CTLN2 is a different disease from classical Citrullinemia Ž . CTLN1; OMIM 215700 caused by a deficiency of a different gene, argininosuccinate synthetase. Some CTLN2 patients might be misdiagnosed as having epilepsy or schizophrenia. Therefore, we emphasize the importance of making a definitive diagnosis at an early stage of the disease by analyzing the SLC25A13 gene.
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Citrullinemia Type II in a 64-year-old man with fluctuating serum citrulline levels.
Journal of the neurological sciences, 2001Co-Authors: Hirofumi Maruyama, Masafumi Ogawa, Takeshi Nishio, Keiko Kobayashi, Takeyori Saheki, Nobuhiko SunoharaAbstract:Abstract We describe a 64-year-old man with ‘Citrullinemia Type II’ whose serum citrulline levels fluctuated between normal and abnormally high during episodic manifesting periods. Elevations of the serum threonine/serine ratio and pancreatic secretory trypsin inhibitor level are very useful diagnostic markers. Our patient’s cerebrospinal fluid citrulline level was also elevated, and T1-weighted magnetic resonance images revealed high-intensity signals at the bilateral internal capsule and the cerebral peduncles. Single-photon emission computed tomography of his brain showed reduced bilateral temporal lobar blood flow. Even if the serum citrulline level is within the normal range, Citrullinemia should be considered in adult patients without primary liver dysfunction who show episodic consciousness disturbance, psychotic symptoms or both.
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Pancreatic secretory trypsin inhibitor gene is highly expressed in the liver of adult-onset Type II Citrullinemia
FEBS letters, 1995Co-Authors: Keiko Kobayashi, Masanori Nakata, Hiroki Terazono, Takuro Shinsato, Takeyori SahekiAbstract:Deficiency of argininosuccinate synthetase (ASS) causes Citrullinemia. Type II Citrullinemia is found in most patients with adult-onset Citrullinemia in Japan, and ASS is deficient specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there are no apparent abnormalities in the amount, translational activity, and nucleotide sequence of hepatic ASS mRNA. Recent results of homozygosity testing indicate that the primary defect of Type II Citrullinemia is not within the ASS gene locus. In this present work, to understand the pathogenesis and pathophysiology of Type II Citrullinemia, we have characterized the alterations of gene expression in the liver of Type II patients using the recently developed mRNA differential display method. Some cDNA bands expressed differently in Type II Citrullinemia patients and control were selected, cloned, and sequenced. Nucleotide sequence analysis and homology searching revealed an interesting clone which has 99% homology with the human pancreatic secretory trypsin inhibitor (hPSTI). Northern blot and RT-PCR analyses showed that the expression of hPSTI mRNA increased significantly in the liver of all Type II patients tested. Furthermore, the concentration of hPSTI protein was found to be higher in the liver of Type II Citrullinemia than in control. These results suggest that hPSTI may be related to the primary defect of Type II Citrullinemia and may be useful as a diagnostic marker, although the detailed mechanism of the high expression of hPSTI mRNA in Type II liver is not yet known.
Nobuhiko Sunohara - One of the best experts on this subject based on the ideXlab platform.
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Citrullinemia Type II in a 64-year-old man with fluctuating serum citrulline levels: mutations in the SLC25A13 gene.
Journal of the neurological sciences, 2001Co-Authors: Hirofumi Maruyama, Masafumi Ogawa, Takeshi Nishio, Keiko Kobayashi, Takeyori Saheki, Nobuhiko SunoharaAbstract:Ž . Citrullinemia Type II CTLN2; OMIM 603471 is caused by the abnormality of the SLC25A13 gene, which encodes a calcium-binding mitochondrial carrier protein, designated w x citrin 1 . We reported a 64-year-old man with CTLN2 whose serum citrulline levels fluctuated between normal and abnormally high during episodic manifesting periods w x 2 . After publication, we obtained informed consent from the patient’s family to perform genetic diagnosis. DNA analysis of the SLC25A13 gene showed that the patient was a compound heterozygote for two known mutations, w x IVS11q1 G)A and IVS13q1 G)A 1 . Such a comw x bination is relatively rare 3 . The mutations, located at the 5 end of each intron, cause abnormal splicing and deletion Ž . of each exon 11 and 13 and result in the destruction of the mitochondrial transmembrane spanning structures of w x citrin 1,3 . It remains to be determined whether the clinical characteristics and prognosis of CTLN2 differ according to the Type of mutation. Though the prognosis is poor, liver transplantation at an early stage of the disease may prevent brain involvement. CTLN2 is a different disease from classical Citrullinemia Ž . CTLN1; OMIM 215700 caused by a deficiency of a different gene, argininosuccinate synthetase. Some CTLN2 patients might be misdiagnosed as having epilepsy or schizophrenia. Therefore, we emphasize the importance of making a definitive diagnosis at an early stage of the disease by analyzing the SLC25A13 gene.
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Citrullinemia Type II in a 64-year-old man with fluctuating serum citrulline levels.
Journal of the neurological sciences, 2001Co-Authors: Hirofumi Maruyama, Masafumi Ogawa, Takeshi Nishio, Keiko Kobayashi, Takeyori Saheki, Nobuhiko SunoharaAbstract:Abstract We describe a 64-year-old man with ‘Citrullinemia Type II’ whose serum citrulline levels fluctuated between normal and abnormally high during episodic manifesting periods. Elevations of the serum threonine/serine ratio and pancreatic secretory trypsin inhibitor level are very useful diagnostic markers. Our patient’s cerebrospinal fluid citrulline level was also elevated, and T1-weighted magnetic resonance images revealed high-intensity signals at the bilateral internal capsule and the cerebral peduncles. Single-photon emission computed tomography of his brain showed reduced bilateral temporal lobar blood flow. Even if the serum citrulline level is within the normal range, Citrullinemia should be considered in adult patients without primary liver dysfunction who show episodic consciousness disturbance, psychotic symptoms or both.
Duangrurdee Wattanasirichaigoon - One of the best experts on this subject based on the ideXlab platform.
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Genetic Analysis of Peroxisomal Genes Required for Longevity in a Yeast Model of Citrin Deficiency
Diseases (Basel Switzerland), 2020Co-Authors: Chalongchai Chalermwat, Thitipa Thosapornvichai, Laran T. Jensen, Duangrurdee WattanasirichaigoonAbstract:Citrin is a liver-specific mitochondrial aspartate-glutamate carrier encoded by SLC25A13. Citrin deficiency caused by SLC25A13 mutation results in carbohydrate toxicity, Citrullinemia Type II, and fatty liver diseases, the mechanisms of some of which remain unknown. Citrin shows a functional homolog in yeast aspartate-glutamate carrier (Agc1p) and agc1Δ yeasts are used as a model organism of citrin deficiency. Here, we found that agc1Δ yeasts decreased fat utilization, impaired NADH balance in peroxisomes, and decreased chronological lifespan. The activation of GPD1-mediated NAD+ regeneration in peroxisomes by GPD1 over-expression or activation of the malate-oxaloacetate NADH peroxisomal shuttle, by increasing flux in this NADH shuttle and over-expression of MDH3, resulted in lifespan extension of agc1Δ yeasts. In addition, over-expression of PEX34 restored longevity of agc1Δ yeasts as well as wild-Type cells. The effect of PEX34-mediated longevity required the presence of the GPD1-mediated NADH peroxisomal shuttle, which was independent of the presence of the peroxisomal malate-oxaloacetate NADH shuttle and PEX34-induced peroxisome proliferation. These data confirm that impaired NAD+ regeneration in peroxisomes is a key defect in the yeast model of citrin deficiency, and enhancing peroxisome function or inducing NAD+ regeneration in peroxisomes is suggested for further study in patients' hepatocytes.
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Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among thai infants
BMC gastroenterology, 2012Co-Authors: Suporn Treepongkaruna, Keiko Kobayashi, Suttiruk Jitraruch, Porawee Kodcharin, Dussadee Charoenpipop, Pim Suwannarat, Paneeya Pienvichit, Duangrurdee WattanasirichaigoonAbstract:Background The most common causes of cholestatic jaundice are biliary atresia and idiopathic neonatal hepatitis (INH). Specific disorders underlying INH, such as various infectious and metabolic causes, including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) especially, in East Asian populations are increasingly being identified. Since most NICCD infants recovered from liver disease by 1 year of age, they often are misdiagnosed with INH, leading to difficulty in determining the true prevalence of NICCD. Mutation(s) of human SLC25A13 gene encoding a mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), can lead to AGC2 deficiency, resulting in NICCD and an adult-onset fatal disease namely Citrullinemia Type II (CTLN2). To study the prevalence of NICCD and SLC25A13 mutations in Thai infants, and to compare manifestations of NICCD and non-NICCD, infants with idiopathic cholestatic jaundice or INH were enrolled. Clinical and biochemical data were reviewed. Urine organic acid and plasma amino acids profiles were analyzed. PCR-sequencing of all 18 exons of SLC25A13 and gap PCR for the mutations IVS16ins3kb and Ex16+74_IVS17-32del516 were performed. mRNA were analyzed in selected cases with possible splicing error.
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Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13mutations among thai infants
BMC Gastroenterology, 2012Co-Authors: Suporn Treepongkaruna, Keiko Kobayashi, Suttiruk Jitraruch, Porawee Kodcharin, Dussadee Charoenpipop, Pim Suwannarat, Paneeya Pienvichit, Duangrurdee WattanasirichaigoonAbstract:Background The most common causes of cholestatic jaundice are biliary atresia and idiopathic neonatal hepatitis (INH). Specific disorders underlying INH, such as various infectious and metabolic causes, including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) especially, in East Asian populations are increasingly being identified. Since most NICCD infants recovered from liver disease by 1 year of age, they often are misdiagnosed with INH, leading to difficulty in determining the true prevalence of NICCD. Mutation(s) of human SLC25A13 gene encoding a mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), can lead to AGC2 deficiency, resulting in NICCD and an adult-onset fatal disease namely Citrullinemia Type II (CTLN2). To study the prevalence of NICCD and SLC25A13 mutations in Thai infants, and to compare manifestations of NICCD and non-NICCD, infants with idiopathic cholestatic jaundice or INH were enrolled. Clinical and biochemical data were reviewed. Urine organic acid and plasma amino acids profiles were analyzed. PCR-sequencing of all 18 exons of SLC25A13 and gap PCR for the mutations IVS16ins3kb and Ex16+74_IVS17-32del516 were performed. mRNA were analyzed in selected cases with possible splicing error. Results Five out of 39 (12.8%) unrelated infants enrolled in the study were found to have NICCD, of which three had homozygous 851del4 (GTATdel) and two compound heterozygous 851del4/IVS16ins3kb and 851del4/1638ins23, respectively. Two missense mutations (p.M1? and p.R605Q) of unknown functional significance were identified. At the initial presentation, NICCD patients had higher levels of alkaline phosphatase (ALP) and alpha-fetoprotein (AFP) and lower level of alanine aminotransferase (ALT) than those in non-NICCD patients ( p < 0.05). NICCD patients showed higher citrulline level and threonine/serine ratio than non-NICCD infants ( p < 0.05). Fatty liver was found in 2 NICCD patients. Jaundice resolved in all NICCD and in 87.5% of non-NICCD infants at the median age of 9.5 and 4.0 months, respectively. Conclusion NICCD should be considered in infants with idiopathic cholestasis. The preliminary estimated prevalence of NICCD was calculated to be 1/48,228 with carrier rate of 1/110 among Thai infants. However, this number may be underestimated and required further analysis with mutation screening in larger control population to establish the true prevalence of NICCD and AGC2 deficiency.
Hirofumi Maruyama - One of the best experts on this subject based on the ideXlab platform.
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Citrullinemia Type II in a 64-year-old man with fluctuating serum citrulline levels: mutations in the SLC25A13 gene.
Journal of the neurological sciences, 2001Co-Authors: Hirofumi Maruyama, Masafumi Ogawa, Takeshi Nishio, Keiko Kobayashi, Takeyori Saheki, Nobuhiko SunoharaAbstract:Ž . Citrullinemia Type II CTLN2; OMIM 603471 is caused by the abnormality of the SLC25A13 gene, which encodes a calcium-binding mitochondrial carrier protein, designated w x citrin 1 . We reported a 64-year-old man with CTLN2 whose serum citrulline levels fluctuated between normal and abnormally high during episodic manifesting periods w x 2 . After publication, we obtained informed consent from the patient’s family to perform genetic diagnosis. DNA analysis of the SLC25A13 gene showed that the patient was a compound heterozygote for two known mutations, w x IVS11q1 G)A and IVS13q1 G)A 1 . Such a comw x bination is relatively rare 3 . The mutations, located at the 5 end of each intron, cause abnormal splicing and deletion Ž . of each exon 11 and 13 and result in the destruction of the mitochondrial transmembrane spanning structures of w x citrin 1,3 . It remains to be determined whether the clinical characteristics and prognosis of CTLN2 differ according to the Type of mutation. Though the prognosis is poor, liver transplantation at an early stage of the disease may prevent brain involvement. CTLN2 is a different disease from classical Citrullinemia Ž . CTLN1; OMIM 215700 caused by a deficiency of a different gene, argininosuccinate synthetase. Some CTLN2 patients might be misdiagnosed as having epilepsy or schizophrenia. Therefore, we emphasize the importance of making a definitive diagnosis at an early stage of the disease by analyzing the SLC25A13 gene.
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Citrullinemia Type II in a 64-year-old man with fluctuating serum citrulline levels.
Journal of the neurological sciences, 2001Co-Authors: Hirofumi Maruyama, Masafumi Ogawa, Takeshi Nishio, Keiko Kobayashi, Takeyori Saheki, Nobuhiko SunoharaAbstract:Abstract We describe a 64-year-old man with ‘Citrullinemia Type II’ whose serum citrulline levels fluctuated between normal and abnormally high during episodic manifesting periods. Elevations of the serum threonine/serine ratio and pancreatic secretory trypsin inhibitor level are very useful diagnostic markers. Our patient’s cerebrospinal fluid citrulline level was also elevated, and T1-weighted magnetic resonance images revealed high-intensity signals at the bilateral internal capsule and the cerebral peduncles. Single-photon emission computed tomography of his brain showed reduced bilateral temporal lobar blood flow. Even if the serum citrulline level is within the normal range, Citrullinemia should be considered in adult patients without primary liver dysfunction who show episodic consciousness disturbance, psychotic symptoms or both.