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George F Grady - One of the best experts on this subject based on the ideXlab platform.

  • tandem mass spectrometric analysis for amino organic and fatty acid disorders in newborn dried blood spots a two year summary from the new england newborn screening program
    Clinical Chemistry, 2001
    Co-Authors: Thomas H Zytkovicz, Eileen F Fitzgerald, Deborah Marsden, Cecilia Larson, Vivian E Shih, Donna M Johnson, Arnold W Strauss, Anne Marie Comeau, Roger B Eaton, George F Grady
    Abstract:

    BACKGROUND: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. METHODS: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in approximately 1.9 min. Cutoffs for each marker were set at 6-13 SD above the population mean. RESULTS: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 Argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. CONCLUSIONS: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.

  • tandem mass spectrometric analysis for amino organic and fatty acid disorders in newborn dried blood spots a two year summary from the new england newborn screening program
    Clinical Chemistry, 2001
    Co-Authors: Thomas H Zytkovicz, Eileen F Fitzgerald, Vivian E Shih, Arnold W Strauss, Anne Marie Comeau, Deborah Marsde, Cecilia Larso, Donna M Johnso, Roge Eato, George F Grady
    Abstract:

    Background: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. Methods: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in ∼1.9 min. Cutoffs for each marker were set at 6–13 SD above the population mean. Results: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 Argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. Conclusions: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.

Thomas H Zytkovicz - One of the best experts on this subject based on the ideXlab platform.

  • tandem mass spectrometric analysis for amino organic and fatty acid disorders in newborn dried blood spots a two year summary from the new england newborn screening program
    Clinical Chemistry, 2001
    Co-Authors: Thomas H Zytkovicz, Eileen F Fitzgerald, Deborah Marsden, Cecilia Larson, Vivian E Shih, Donna M Johnson, Arnold W Strauss, Anne Marie Comeau, Roger B Eaton, George F Grady
    Abstract:

    BACKGROUND: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. METHODS: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in approximately 1.9 min. Cutoffs for each marker were set at 6-13 SD above the population mean. RESULTS: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 Argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. CONCLUSIONS: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.

  • tandem mass spectrometric analysis for amino organic and fatty acid disorders in newborn dried blood spots a two year summary from the new england newborn screening program
    Clinical Chemistry, 2001
    Co-Authors: Thomas H Zytkovicz, Eileen F Fitzgerald, Vivian E Shih, Arnold W Strauss, Anne Marie Comeau, Deborah Marsde, Cecilia Larso, Donna M Johnso, Roge Eato, George F Grady
    Abstract:

    Background: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. Methods: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in ∼1.9 min. Cutoffs for each marker were set at 6–13 SD above the population mean. Results: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 Argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. Conclusions: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.

Ichiro Matsuda - One of the best experts on this subject based on the ideXlab platform.

  • Molecular basis of phenotypic variation in patients with Argininemia
    Human Genetics, 1995
    Co-Authors: Takako Uchino, Selma E. Snyderman, Marie Lambert, Ijaz A. Qureshi, Stuart K. Shapira, Claude Sansaricq, Leonard M. E. Smit, Cornelis Jakobs, Ichiro Matsuda
    Abstract:

    Argininemia is an autosomal recessive disorder caused by a deficiency in the liver-type arginase enzyme. Clinical manifestations include progressive spastic diplegia and mental retardation. While the quality of life can severely deteriorate in most such patients, some do show remarkable improvement in neurological symptoms while on controlled diets. We examined the thesis that differences in clinical responses to dietary treatment are based on molecular heterogeneity in mutant arginase alleles. Genomic DNAs from 11 patients with Argininemia were examined using the polymerase chain reaction, cloning, and sequencing. Nine mutations representing 21/22 mutant alleles were identified in 11 patients with Argininemia, and four of these mutations were expressed in vitro to determine the severity of enzymatic defects. We found that these mutations accounted for 64% of the mutant alleles in our patients. Based on findings in vitro expression tests, the mutations can be considered either severe or moderate. Patients with at least one moderate mutant allele responded well to dietary treatment; concentrations of plasma arginine were controlled within 300 μ M . In contrast, patients with two severely mutated alleles did not respond to dietary treatment and plasma arginine was over 400 μ M . Argininemia is heterogeneous at the molecular level. The degree of clinical improvement during dietary treatment is reflected in the concentration of arginine in plasma, as a measure of metabolic control. Plasma arginine levels during treatment is reflected in the concentration of arginine in plasma, as a measure of metabolic control. Plasma arginine levels during treatment correlated with types of molecular defects in the arginase genes.

  • three novel mutations in the liver type arginase gene in three unrelated japanese patients with Argininemia
    American Journal of Human Genetics, 1992
    Co-Authors: T Uchino, Y Haraguchi, J M Aparicio, N Mizutani, M Higashikawa, H Naitoh, M Mori, Ichiro Matsuda
    Abstract:

    Abstract Argininemia is caused by a hereditary deficiency of liver-type arginase (E.C.3.5.3.1) and is characterized by psychomotor retardation and spastic tetraplegia. We examined findings in three Japanese patients with Argininemia, by using the PCR, cloning, and sequencing procedures. We found three different mutations--G-to-A-365 in exon 4, G-to-C-703 in exon 7, and C-del-842 in exon 8--thereby leading to mutant arginase proteins of W122X, G235R, and L282FS, respectively. Patient 1 was a compound heterozygote, inheriting the allele with G-to-A-365 from his mother and the allele with G-to-C-703 from his father. Patients 2 and 3 were homozygotes of the allele with G-to-C-703 and of the allele with C-del-842, respectively. Expression tests of these mutant arginases in Escherichia coli indicated that the mutant arginase of W122X did not remain a stable product. The other two mutant arginases--G235R and L282FS--were detected by immunoblot analyses. There was no evidence of activity of the three mutant arginases expressed in E. coli. We tentatively conclude that Argininemia is heterogeneous, at the molecular level.

Anne Marie Comeau - One of the best experts on this subject based on the ideXlab platform.

  • tandem mass spectrometric analysis for amino organic and fatty acid disorders in newborn dried blood spots a two year summary from the new england newborn screening program
    Clinical Chemistry, 2001
    Co-Authors: Thomas H Zytkovicz, Eileen F Fitzgerald, Deborah Marsden, Cecilia Larson, Vivian E Shih, Donna M Johnson, Arnold W Strauss, Anne Marie Comeau, Roger B Eaton, George F Grady
    Abstract:

    BACKGROUND: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. METHODS: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in approximately 1.9 min. Cutoffs for each marker were set at 6-13 SD above the population mean. RESULTS: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 Argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. CONCLUSIONS: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.

  • tandem mass spectrometric analysis for amino organic and fatty acid disorders in newborn dried blood spots a two year summary from the new england newborn screening program
    Clinical Chemistry, 2001
    Co-Authors: Thomas H Zytkovicz, Eileen F Fitzgerald, Vivian E Shih, Arnold W Strauss, Anne Marie Comeau, Deborah Marsde, Cecilia Larso, Donna M Johnso, Roge Eato, George F Grady
    Abstract:

    Background: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. Methods: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in ∼1.9 min. Cutoffs for each marker were set at 6–13 SD above the population mean. Results: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 Argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. Conclusions: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.

Arnold W Strauss - One of the best experts on this subject based on the ideXlab platform.

  • tandem mass spectrometric analysis for amino organic and fatty acid disorders in newborn dried blood spots a two year summary from the new england newborn screening program
    Clinical Chemistry, 2001
    Co-Authors: Thomas H Zytkovicz, Eileen F Fitzgerald, Deborah Marsden, Cecilia Larson, Vivian E Shih, Donna M Johnson, Arnold W Strauss, Anne Marie Comeau, Roger B Eaton, George F Grady
    Abstract:

    BACKGROUND: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. METHODS: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in approximately 1.9 min. Cutoffs for each marker were set at 6-13 SD above the population mean. RESULTS: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 Argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. CONCLUSIONS: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.

  • tandem mass spectrometric analysis for amino organic and fatty acid disorders in newborn dried blood spots a two year summary from the new england newborn screening program
    Clinical Chemistry, 2001
    Co-Authors: Thomas H Zytkovicz, Eileen F Fitzgerald, Vivian E Shih, Arnold W Strauss, Anne Marie Comeau, Deborah Marsde, Cecilia Larso, Donna M Johnso, Roge Eato, George F Grady
    Abstract:

    Background: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. Methods: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in ∼1.9 min. Cutoffs for each marker were set at 6–13 SD above the population mean. Results: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 Argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. Conclusions: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.