The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform
Lee-jun C. Wong - One of the best experts on this subject based on the ideXlab platform.
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Neonatal presentation of ventricular tachycardia and a Reye-like syndrome episode associated with disturbed mitochondrial energy metabolism
BMC pediatrics, 2002Co-Authors: Fernando Scaglia, Lawrence Sweetman, Angela E. Scheuerle, Jeffrey A. Towbin, Dawna L. Armstrong, Lee-jun C. WongAbstract:Hyperammonemia, hypoglycemia, hepatopathy, and ventricular tachycardia are common presenting features of carnitine-acylcarnitine translocase deficiency (Mendelian Inheritance in Man database: *212138), a mitochondrial fatty acid oxidation disorder with a lethal prognosis. These features have not been identified as the presenting features of mitochondrial cytopathy in the neonatal period. We describe an atypical presentation of mitochondrial cytopathy in a 2 day-old neonate. She presented with a Reye-like syndrome episode, premature ventricular contractions and ventricular tachycardia. Initial laboratory evaluation exhibited a large amount of 3-methylglutaconic acid on urine organic acid analysis, mild Orotic Aciduria and a nonspecific abnormal acylcarnitine profile. The evaluation for carnitine-acylcarnitine translocase deficiency and other fatty acid oxidation disorders was negative. The patient later developed a hypertrophic cardiomyopathy and continued to be affected by recurrent Reye-like syndrome episodes triggered by infections. A muscle biopsy exhibited signs of a mitochondrial cytopathy. During the course of her disease, her Reye-like syndrome episodes have subsided; however, cardiomyopathy has persisted along with fatigue and exercise intolerance. This case illustrates that, in the neonatal period, hyperammonemia and ventricular tachycardia may be the presenting features of a lethal carnitine-acylcarnitine translocase deficiency or of a mitochondrial cytopathy, associated with a milder clinical course. This association broadens the spectrum of presenting phenotypes observed in patients with disturbed mitochondrial energy metabolism. Also, the presence of 3-methylglutaconic Aciduria suggests mitochondrial dysfunction and mild Orotic Aciduria could potentially be used as a marker of mitochondrial disease.
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Neonatal presentation of ventricular tachycardia and a Reye-like syndrome episode associated with disturbed mitochondrial energy metabolism
BMC Pediatrics, 2002Co-Authors: Fernando Scaglia, Lawrence Sweetman, Angela E. Scheuerle, Jeffrey A. Towbin, Dawna L. Armstrong, Lee-jun C. WongAbstract:Background Hyperammonemia, hypoglycemia, hepatopathy, and ventricular tachycardia are common presenting features of carnitine-acylcarnitine translocase deficiency (Mendelian Inheritance in Man database: *212138), a mitochondrial fatty acid oxidation disorder with a lethal prognosis. These features have not been identified as the presenting features of mitochondrial cytopathy in the neonatal period. Case presentation We describe an atypical presentation of mitochondrial cytopathy in a 2 day-old neonate. She presented with a Reye-like syndrome episode, premature ventricular contractions and ventricular tachycardia. Initial laboratory evaluation exhibited a large amount of 3-methylglutaconic acid on urine organic acid analysis, mild Orotic Aciduria and a nonspecific abnormal acylcarnitine profile. The evaluation for carnitine-acylcarnitine translocase deficiency and other fatty acid oxidation disorders was negative. The patient later developed a hypertrophic cardiomyopathy and continued to be affected by recurrent Reye-like syndrome episodes triggered by infections. A muscle biopsy exhibited signs of a mitochondrial cytopathy. During the course of her disease, her Reye-like syndrome episodes have subsided; however, cardiomyopathy has persisted along with fatigue and exercise intolerance. Conclusions This case illustrates that, in the neonatal period, hyperammonemia and ventricular tachycardia may be the presenting features of a lethal carnitine-acylcarnitine translocase deficiency or of a mitochondrial cytopathy, associated with a milder clinical course. This association broadens the spectrum of presenting phenotypes observed in patients with disturbed mitochondrial energy metabolism. Also, the presence of 3-methylglutaconic Aciduria suggests mitochondrial dysfunction and mild Orotic Aciduria could potentially be used as a marker of mitochondrial disease.
Yoshiro Wada - One of the best experts on this subject based on the ideXlab platform.
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Decreased fluorouracil cytotoxic effect on EB-virus transformed lymphocytes from hereditary Orotic Aciduria.
International journal of molecular medicine, 2000Co-Authors: M Andou, Hajime Togari, Satoshi Sumi, Yoshiro WadaAbstract:5-Fluorouracil (5-FU), used widely for malignancies, phosphorylate mostly by uracil phosphoribosyl transferase (UPRT). Patients with hereditary Orotic Aciduria lack the orotate phosphoribosyl transferase (OPRT) activity. In the cancer cells, the OPRT activity is paralleled with the UPRT activity. This study shows that the UPRT activity of the hereditary Orotic Aciduria homozygote decreased about 40% of normal controls. Moreover, we investigated the 5-FU cytotoxic effects on hereditary Orotic Aciduria (one homozygote, 4 heterozygotes and 7 normal controls), using EB-virus transformed lymphocytes (EB-LC). 5-FU was addded to the culture medium at concentrations ranging from 0 to 10.0 micromol/l. The 5-FU cytotoxic effects on the homozygote were milder than those on controls at each 5-FU concentration. The 5-FU cytotoxic effects in the heterozygotes were at intermediate levels between the homozygote and controls. We speculate that 5-FU cytotoxic effects, both anti-tumor effects and adverse reactions, would be weak when a patient with hereditary Orotic Aciduria was treated with 5-FU.
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Hereditary Orotic Aciduria Heterozygotes Accompanied with Neurological Symptoms
The Tohoku journal of experimental medicine, 1998Co-Authors: Masayuki Imaeda, Satoshi Sumi, Kiyoshi Kidouchi, Hiromi Imaeda, Mariko Suchi, Hajime Togari, Yoshiro WadaAbstract:We report a family with hereditary Orotic Aciduria heterozygotes. A 3-year-old boy who had been diagnosed as having cerebral palsy and mental retardation presented himself with an increase in excretion of urinary Orotic acid. Enzymatic studies revealed that the boy and his healthy mother were hereditary Orotic Aciduria heterozygote carriers. We can not prove that this pyrimidine disorder caused his neurological symptoms, but his pyrimidine nucleoside supply may have been insufficient in his neonatal period.
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molecular cloning of the human ump synthase gene and characterization of point mutations in two hereditary Orotic Aciduria families
American Journal of Human Genetics, 1997Co-Authors: Mariko Suchi, Satoshi Sumi, Haruo Mizuno, Yoko Kawai, Takashi Tsuboi, Kazuki Okajima, Mark E Hodgson, Hisamitsu Ogawa, Yoshiro WadaAbstract:Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC). Loss of either enzymatic activity results in hereditary Orotic Aciduria, a rare autosomal recessive disorder characterized by retarded growth, anemia, and excessive urinary excretion of Orotic acid. We have isolated the UMP synthase chromosomal gene from a lambdaEMBL-3 human genomic library and report a single-copy gene spanning approximately 15 kb. The UMP synthase genomic structure encodes six exons ranging in size from 115 bp to 672 bp, and all splicing junctions adhere to the canonical GT/AG rule. Cognate promoter elements implicated in glucocorticoid- and cAMP-mediated regulation as well as in liver-, myeloid-, and lymphocyte-specific expression are located within the 5' flanking sequence. Molecular investigation of UMP synthase deficiency in a Japanese Orotic Aciduria patient revealed mutations R96G (A-to-G transition; nt 286) and G429R (G-to-C transversion; nt 1285) in one allele and V109G (T-to-G transversion; nt 326) in the other allele. Expression of human UMP synthase cDNAs containing these mutations in pyrimidine auxotrophic Escherichia coli and in recombinant baculovirus-infected Sf21 cells demonstrates impaired activity presumably associated with the urinary Orotic acid substrate accumulations observed in vivo. We further establish the identity of two polymorphisms, G213A (v = .26) and 440Gpoly (v = .27) located in exons 3 and 6, respectively, which did not significantly compromise either OPRT or ODC function.
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Automated screening system for purine and pyrimidine metabolism disorders using high-performance liquid chromatography.
Journal of Chromatography B: Biomedical Sciences and Applications, 1995Co-Authors: Satoshi Sumi, Kiyoshi Kidouchi, Satoru Ohba, Yoshiro WadaAbstract:An automated screening system for purine and pyrimidine metabolism disorders using high-performance liquid chromatography (HPLC) with column switching is described. The system consists of a reversed-phase column, a cation-exchange column, a column switch, four sets of ultraviolet absorbance detectors, a microcomputer and other conventional equipment. As this system permits the simultaneous determination of urinary Orotic acid, uracil, dihydrouracil, pseudouridine, xanthine, 2,8-dihydroxyadenine and succinyladenosine, it offers a useful method for the detection of Orotic Aciduria, dihydropyrimidine dehydrogenase deficiency, diphydropyrimidinuria, xanthinuria, adenine phosphoribosyltransferase deficiency and adenylosuccinase deficiency.
Fernando Scaglia - One of the best experts on this subject based on the ideXlab platform.
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Neonatal presentation of ventricular tachycardia and a Reye-like syndrome episode associated with disturbed mitochondrial energy metabolism
BMC pediatrics, 2002Co-Authors: Fernando Scaglia, Lawrence Sweetman, Angela E. Scheuerle, Jeffrey A. Towbin, Dawna L. Armstrong, Lee-jun C. WongAbstract:Hyperammonemia, hypoglycemia, hepatopathy, and ventricular tachycardia are common presenting features of carnitine-acylcarnitine translocase deficiency (Mendelian Inheritance in Man database: *212138), a mitochondrial fatty acid oxidation disorder with a lethal prognosis. These features have not been identified as the presenting features of mitochondrial cytopathy in the neonatal period. We describe an atypical presentation of mitochondrial cytopathy in a 2 day-old neonate. She presented with a Reye-like syndrome episode, premature ventricular contractions and ventricular tachycardia. Initial laboratory evaluation exhibited a large amount of 3-methylglutaconic acid on urine organic acid analysis, mild Orotic Aciduria and a nonspecific abnormal acylcarnitine profile. The evaluation for carnitine-acylcarnitine translocase deficiency and other fatty acid oxidation disorders was negative. The patient later developed a hypertrophic cardiomyopathy and continued to be affected by recurrent Reye-like syndrome episodes triggered by infections. A muscle biopsy exhibited signs of a mitochondrial cytopathy. During the course of her disease, her Reye-like syndrome episodes have subsided; however, cardiomyopathy has persisted along with fatigue and exercise intolerance. This case illustrates that, in the neonatal period, hyperammonemia and ventricular tachycardia may be the presenting features of a lethal carnitine-acylcarnitine translocase deficiency or of a mitochondrial cytopathy, associated with a milder clinical course. This association broadens the spectrum of presenting phenotypes observed in patients with disturbed mitochondrial energy metabolism. Also, the presence of 3-methylglutaconic Aciduria suggests mitochondrial dysfunction and mild Orotic Aciduria could potentially be used as a marker of mitochondrial disease.
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Neonatal presentation of ventricular tachycardia and a Reye-like syndrome episode associated with disturbed mitochondrial energy metabolism
BMC Pediatrics, 2002Co-Authors: Fernando Scaglia, Lawrence Sweetman, Angela E. Scheuerle, Jeffrey A. Towbin, Dawna L. Armstrong, Lee-jun C. WongAbstract:Background Hyperammonemia, hypoglycemia, hepatopathy, and ventricular tachycardia are common presenting features of carnitine-acylcarnitine translocase deficiency (Mendelian Inheritance in Man database: *212138), a mitochondrial fatty acid oxidation disorder with a lethal prognosis. These features have not been identified as the presenting features of mitochondrial cytopathy in the neonatal period. Case presentation We describe an atypical presentation of mitochondrial cytopathy in a 2 day-old neonate. She presented with a Reye-like syndrome episode, premature ventricular contractions and ventricular tachycardia. Initial laboratory evaluation exhibited a large amount of 3-methylglutaconic acid on urine organic acid analysis, mild Orotic Aciduria and a nonspecific abnormal acylcarnitine profile. The evaluation for carnitine-acylcarnitine translocase deficiency and other fatty acid oxidation disorders was negative. The patient later developed a hypertrophic cardiomyopathy and continued to be affected by recurrent Reye-like syndrome episodes triggered by infections. A muscle biopsy exhibited signs of a mitochondrial cytopathy. During the course of her disease, her Reye-like syndrome episodes have subsided; however, cardiomyopathy has persisted along with fatigue and exercise intolerance. Conclusions This case illustrates that, in the neonatal period, hyperammonemia and ventricular tachycardia may be the presenting features of a lethal carnitine-acylcarnitine translocase deficiency or of a mitochondrial cytopathy, associated with a milder clinical course. This association broadens the spectrum of presenting phenotypes observed in patients with disturbed mitochondrial energy metabolism. Also, the presence of 3-methylglutaconic Aciduria suggests mitochondrial dysfunction and mild Orotic Aciduria could potentially be used as a marker of mitochondrial disease.
C. J. Bailey - One of the best experts on this subject based on the ideXlab platform.
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Orotic Aciduria and uridine monophosphate synthase: a reappraisal.
Journal of Inherited Metabolic Disease, 2009Co-Authors: C. J. BaileyAbstract:Three subtypes of hereditary Orotic Aciduria are described in the literature, all related to deficiencies in uridine monophosphate synthase, the multifunctional enzyme that contains both orotate: pyrophosphoryl transferase and orotidine monophosphate decarboxylase activities. The type of enzyme defect present in the subtypes has been re-examined by steady-state modelling of the relative outputs of the three enzymic products, uridine monophosphate, urinary Orotic acid and urinary orotidine. It is shown that the ratio of urinary outputs of orotidine to orotate provides a means of testing for particular forms of enzyme defect. It is confirmed that the type I defect is caused by loss of uridine monophosphate synthase activity. Cells and tissue of type I cases have a residual amount of activity that is qualitatively unchanged: the relative rates of the transferase and decarboxylase do not differ from those of wild-type enzyme. The single claimed case of type II, thought to be due to specific inactivation of orotidine monophosphate decarboxylase, is shown to have a product spectrum inconsistent with that claim. It is proposed that this type II form does not differ sufficiently to be accepted as separate from type I. The third subtype, hereditary Orotic Aciduria without megaloblastic anaemia, occurs in two cases. It has the product spectrum expected of a defect in orotidine monophosphate decarboxylase. This form is the only one that appears to have a qualitatively different uridine monophosphate synthase. The possibility that orotidine monophosphate may control flux through the pyrimidine biosynthesis pathway in hereditary Orotic Aciduria is discussed.
Saskia B Wortmann - One of the best experts on this subject based on the ideXlab platform.
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mild Orotic Aciduria in umps heterozygotes a metabolic finding without clinical consequences
Journal of Inherited Metabolic Disease, 2017Co-Authors: Tatiana Yuzyuk, Margaret A Chen, Bader Alhaddad, Alessandro Pontoglio, Saskia B Wortmann, Lorenzo D Botto, Roberto Colombo, Curtis R CoughlinAbstract:Background Elevated urinary excretion of Orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with Orotic Aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary Orotic Aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue.
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mild Orotic Aciduria in umps heterozygotes a metabolic finding without clinical consequences
Journal of Inherited Metabolic Disease, 2017Co-Authors: Tatiana Yuzyuk, Margaret A Chen, Bader Alhaddad, Alessandro Pontoglio, Saskia B Wortmann, Lorenzo D Botto, Roberto Colombo, Curtis R CoughlinAbstract:Background Elevated urinary excretion of Orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with Orotic Aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary Orotic Aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue.