The Experts below are selected from a list of 249 Experts worldwide ranked by ideXlab platform
Anibh M. Das - One of the best experts on this subject based on the ideXlab platform.
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Newborn Screening for Hepatorenal Tyrosinemia: Tandem Mass Spectrometric Quantification of
2015Co-Authors: Friedrich K. Trefz, Anibh M. DasAbstract:Background: False-positive and false-negative results occur in current newborn-screening programs for hepa-torenal tyrosinemia, which measure tyrosine concen-trations in blood spots, sometimes in combination with other metabolites, including Succinylacetone. We present our experience with a newly described method for Succinylacetone quantification in routine newborn screening. Methods: Succinylacetone was extracted from blood spots that had already been extracted with absolute methanol for acylcarnitine and amino acid analysis. The solvent was acetonitrile–water (80:20 by volume) con-taining formic acid, hydrazine hydrate, and 100 nmol/L 5,7-dioxooctanoic acid as internal standard. Analysis was performed by tandem mass spectrometry in a sep
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Newborn Screening for Hepatorenal Tyrosinemia: Tandem Mass Spectrometric Quantification of Succinylacetone
Clinical chemistry, 2006Co-Authors: Johannes Sander, Nils Janzen, Michael Peter, Stefanie Sander, Ulrike Steuerwald, Ute Holtkamp, Bernd Schwahn, Ertan Mayatepek, Friedrich K. Trefz, Anibh M. DasAbstract:Background: False-positive and false-negative results occur in current newborn-screening programs for hepatorenal tyrosinemia, which measure tyrosine concentrations in blood spots, sometimes in combination with other metabolites, including Succinylacetone. We present our experience with a newly described method for Succinylacetone quantification in routine newborn screening. Methods: Succinylacetone was extracted from blood spots that had already been extracted with absolute methanol for acylcarnitine and amino acid analysis. The solvent was acetonitrile–water (80:20 by volume) containing formic acid, hydrazine hydrate, and 100 nmol/L 5,7-dioxooctanoic acid as internal standard. Analysis was performed by tandem mass spectrometry in a separate run. Results: Of 61 344 samples, 99.6% had Succinylacetone concentrations ≤5 μmol/L. With a cutoff of 10 μmol/L, no false-positive results were obtained. In 2 patients, the Succinylacetone concentrations in the dried blood spots from the 36th and 56th hours of life were 152 and 271 μmol/L, respectively, and the tyrosine concentrations were 54 and 129 μmol/L. Hepatorenal tyrosinemia was subsequently confirmed in both patients. Retrospective analysis of the neonatal screening samples of 2 additional known patients revealed increased Succinylacetone concentrations of 46 and 169 μmol/L, respectively. Conclusions: Tandem mass spectrometric quantification directly from residual blood spots is a useful method for the early detection of hepatorenal tyrosinemia in newborn-screening programs.
Ertan Mayatepek - One of the best experts on this subject based on the ideXlab platform.
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Spectrophotometric Microassay for d-Aminolevulinate Dehydratase in Dried-Blood Spots as Confirmation for Hereditary
2015Co-Authors: Tyrosinemia Type, Andreas Schulze, David Frommhold, Georg F. Hoffmann, Ertan MayatepekAbstract:the criteria for inclusion in neonatal screening pro-grams, but measurement of tyrosine lacks clinical spec-ificity and quantitative assay of Succinylacetone is labo-rious. We developed a semiquantitative assay based on inhibition of d-aminolevulinate dehydratase (ALA-D) by Succinylacetone. Methods: Preincubation of 3-mm discs from dried-blood spots and reaction of the enzyme with d-amino-levulinic acid as substrate were performed in microtiter plates. After separation of the supernatant and 10 min of color reaction with modified Ehrlich reagent, the forma-tion of porphobilinogen was measured at 550 nm in a plate reader. Results: The detection limit for Succinylacetone was 0.3 mmol/L; imprecision (CV) was <5.5 % within-run an
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Significant increase of Succinylacetone within the first 12 h of life in hereditary tyrosinemia type 1
European Journal of Pediatrics, 2010Co-Authors: Jan-ulrich Schlump, Ertan Mayatepek, Ute SpiekerkoetterAbstract:Introduction In most countries, hereditary tyrosinemia type 1 is not included in routine newborn screening. Discussion We present the case of a female newborn with prenatal diagnosis of hereditary tyrosinemia type 1 and clear identification of this disorder by Succinylacetone measurement in cord blood and peripheral blood immediately after birth. Succinylacetone was 44 μmol/L (norm
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Newborn Screening for Hepatorenal Tyrosinemia: Tandem Mass Spectrometric Quantification of Succinylacetone
Clinical chemistry, 2006Co-Authors: Johannes Sander, Nils Janzen, Michael Peter, Stefanie Sander, Ulrike Steuerwald, Ute Holtkamp, Bernd Schwahn, Ertan Mayatepek, Friedrich K. Trefz, Anibh M. DasAbstract:Background: False-positive and false-negative results occur in current newborn-screening programs for hepatorenal tyrosinemia, which measure tyrosine concentrations in blood spots, sometimes in combination with other metabolites, including Succinylacetone. We present our experience with a newly described method for Succinylacetone quantification in routine newborn screening. Methods: Succinylacetone was extracted from blood spots that had already been extracted with absolute methanol for acylcarnitine and amino acid analysis. The solvent was acetonitrile–water (80:20 by volume) containing formic acid, hydrazine hydrate, and 100 nmol/L 5,7-dioxooctanoic acid as internal standard. Analysis was performed by tandem mass spectrometry in a separate run. Results: Of 61 344 samples, 99.6% had Succinylacetone concentrations ≤5 μmol/L. With a cutoff of 10 μmol/L, no false-positive results were obtained. In 2 patients, the Succinylacetone concentrations in the dried blood spots from the 36th and 56th hours of life were 152 and 271 μmol/L, respectively, and the tyrosine concentrations were 54 and 129 μmol/L. Hepatorenal tyrosinemia was subsequently confirmed in both patients. Retrospective analysis of the neonatal screening samples of 2 additional known patients revealed increased Succinylacetone concentrations of 46 and 169 μmol/L, respectively. Conclusions: Tandem mass spectrometric quantification directly from residual blood spots is a useful method for the early detection of hepatorenal tyrosinemia in newborn-screening programs.
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spectrophotometric microassay for δ aminolevulinate dehydratase in dried blood spots as confirmation for hereditary tyrosinemia type i
Clinical Chemistry, 2001Co-Authors: Andreas Schulze, David Frommhold, Georg F. Hoffmann, Ertan MayatepekAbstract:Background: Hereditary tyrosinemia type I (HT) fulfills the criteria for inclusion in neonatal screening programs, but measurement of tyrosine lacks clinical specificity and quantitative assay of Succinylacetone is laborious. We developed a semiquantitative assay based on inhibition of δ-aminolevulinate dehydratase (ALA-D) by Succinylacetone. Methods: Preincubation of 3-mm discs from dried-blood spots and reaction of the enzyme with δ-aminolevulinic acid as substrate were performed in microtiter plates. After separation of the supernatant and 10 min of color reaction with modified Ehrlich reagent, the formation of porphobilinogen was measured at 550 nm in a plate reader. Results: The detection limit for Succinylacetone was 0.3 μmol/L; imprecision (CV) was <5.5% within-run and 10–16% between-run. Storage of blood spots at ambient temperature for several days led to a significant decrease of ALA-D activity. Enzyme activity was lost in filter cards at 45 °C, but remained stable at 2–37 °C. Enzyme activity was decreased in EDTA blood. The absorbance at 550 nm was 0.221 (± 0.073) in healthy neonates and 0.043–0.100 in 11 patients with HT. All neonates with increased tyrosine (above the 99.5th centile) in neonatal screening (97 of 47 000) had normal results by the new assay. Conclusions: The spectrophotometric microassay for ALA-D is a simple and sensitive test for HT. This represents a basis for further examination of its general reliability as a confirmatory test if tyrosine is found to be increased.
Uta Ceglarek - One of the best experts on this subject based on the ideXlab platform.
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Tandem mass spectrometric determination of Succinylacetone in dried blood spots enables presymptomatic detection in a case of hepatorenal tyrosinaemia
Journal of inherited metabolic disease, 2007Co-Authors: Johannes F. W. Weigel, N. Janzen, R. W. Pfäffle, Joachim Thiery, Wieland Kiess, Uta CeglarekAbstract:Tyrosinaemia type I, or fumarylacetoacetase deficiency, causes hepatorenal damage by accumulation of fumarylacetoacetate. Patients are generally in good condition at birth, but are at risk of developing serious metabolic crises with liver failure and hepatic coma. An early start of treatment with NTBC and a tyrosine-balanced diet can prevent harm to the patients. The application of tandem mass spectrometry to newborn screening allows for easy determination of tyrosine to detect the presence of hypertyrosinaemia in the neonate, but most patients with tyrosinaemia type I do not present with high tyrosine levels at the time of newborn screening. We report on a 7-week-old girl presenting with acute hepatopathy and severe coagulopathy due to tyrosinaemia type I. The metabolic screening, which was performed by tandem mass spectrometry at the age of 48 h, had revealed normal values for tyrosine and methionine that were well within ranges observed in the general population and equally normal ratios of methionine/tyrosine and tyrosine/serine. In this patient even lowering the cut-off levels for tyrosine and methionine would not have provided better sensitivity. Residual blood spots from the newborn screening filter paper were retrospectively analysed using a specific mass-spectrometric method for the detection of Succinylacetone and revealed a 5-fold elevated Succinylacetone concentration. This indicates that identification of all newborns with hepatorenal tyrosinaemia is only possible by determination of Succinylacetone as part of the newborn screening process.
Víctor R De Jesús - One of the best experts on this subject based on the ideXlab platform.
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simultaneous quantitation of hexacosanoyl lysophosphatidylcholine amino acids acylcarnitines and Succinylacetone during fia esi ms ms analysis of dried blood spot extracts for newborn screening
Clinical Biochemistry, 2016Co-Authors: Christopher A. Haynes, Víctor R De JesúsAbstract:Objectives The goal of this study was to include the quantitation of hexacosanoyl lysophosphatidylcholine, a biomarker for X-linked adrenoleukodystrophy and other peroxisomal disorders, in the routine extraction and analysis procedure used to quantitate amino acids, acylcarnitines, and Succinylacetone during newborn screening. Criteria for the method included use of a single punch from a dried blood spot, one simple extraction of the punch, no high-performance liquid chromatography, and utilizing tandem mass spectrometry to quantitate the analytes.
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Simultaneous quantitation of hexacosanoyl lysophosphatidylcholine, amino acids, acylcarnitines, and Succinylacetone during FIA-ESI-MS/MS analysis of dried blood spot extracts for newborn screening.
Clinical biochemistry, 2015Co-Authors: Christopher A. Haynes, Víctor R De JesúsAbstract:The goal of this study was to include the quantitation of hexacosanoyl lysophosphatidylcholine, a biomarker for X-linked adrenoleukodystrophy and other peroxisomal disorders, in the routine extraction and analysis procedure used to quantitate amino acids, acylcarnitines, and Succinylacetone during newborn screening. Criteria for the method included use of a single punch from a dried blood spot, one simple extraction of the punch, no high-performance liquid chromatography, and utilizing tandem mass spectrometry to quantitate the analytes. Dried blood spot punches were extracted with a methanolic solution of stable-isotope labeled internal standards, formic acid, and hydrazine, followed by flow injection analysis-electrospray ionization-tandem mass spectrometry. Quantitation of amino acids, acylcarnitines, and hexacosanoyl lysophosphatidylcholine using this combined method was similar to results obtained using two separate methods. A single dried blood spot punch extracted by a rapid (45min), simple procedure can be analyzed with high throughput (2min per sample) to quantitate amino acids, acylcarnitines, Succinylacetone, and hexacosanoyl lysophosphatidylcholine. Published by Elsevier Inc.
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Simultaneous quantitation of hexacosanoyl lysophosphatidylcholine, amino acids, acylcarnitines, and Succinylacetone during FIA–ESI–MS/MS analysis of dried blood spot extracts for newborn screening
Clinical Biochemistry, 2015Co-Authors: Christopher A. Haynes, Víctor R De JesúsAbstract:Objectives The goal of this study was to include the quantitation of hexacosanoyl lysophosphatidylcholine, a biomarker for X-linked adrenoleukodystrophy and other peroxisomal disorders, in the routine extraction and analysis procedure used to quantitate amino acids, acylcarnitines, and Succinylacetone during newborn screening. Criteria for the method included use of a single punch from a dried blood spot, one simple extraction of the punch, no high-performance liquid chromatography, and utilizing tandem mass spectrometry to quantitate the analytes.
Johannes Sander - One of the best experts on this subject based on the ideXlab platform.
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Newborn Screening for Hepatorenal Tyrosinemia: Tandem Mass Spectrometric Quantification of Succinylacetone
Clinical chemistry, 2006Co-Authors: Johannes Sander, Nils Janzen, Michael Peter, Stefanie Sander, Ulrike Steuerwald, Ute Holtkamp, Bernd Schwahn, Ertan Mayatepek, Friedrich K. Trefz, Anibh M. DasAbstract:Background: False-positive and false-negative results occur in current newborn-screening programs for hepatorenal tyrosinemia, which measure tyrosine concentrations in blood spots, sometimes in combination with other metabolites, including Succinylacetone. We present our experience with a newly described method for Succinylacetone quantification in routine newborn screening. Methods: Succinylacetone was extracted from blood spots that had already been extracted with absolute methanol for acylcarnitine and amino acid analysis. The solvent was acetonitrile–water (80:20 by volume) containing formic acid, hydrazine hydrate, and 100 nmol/L 5,7-dioxooctanoic acid as internal standard. Analysis was performed by tandem mass spectrometry in a separate run. Results: Of 61 344 samples, 99.6% had Succinylacetone concentrations ≤5 μmol/L. With a cutoff of 10 μmol/L, no false-positive results were obtained. In 2 patients, the Succinylacetone concentrations in the dried blood spots from the 36th and 56th hours of life were 152 and 271 μmol/L, respectively, and the tyrosine concentrations were 54 and 129 μmol/L. Hepatorenal tyrosinemia was subsequently confirmed in both patients. Retrospective analysis of the neonatal screening samples of 2 additional known patients revealed increased Succinylacetone concentrations of 46 and 169 μmol/L, respectively. Conclusions: Tandem mass spectrometric quantification directly from residual blood spots is a useful method for the early detection of hepatorenal tyrosinemia in newborn-screening programs.
