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Kinder- und Jugendmedizin 2012; 12(02): 104-108
DOI: 10.1055/s-0038-1629184
Neugeborenenscreening
Schattauer GmbH

Entwicklungen und Trends massenspektrometrischer Applikationen für das Neugeborenenscreening

Trends and developments of mass spectrometric applications in newborn screening
U. Ceglarek
1   Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik, Universitätsklinikum Leipzig
,
S. Becker
1   Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik, Universitätsklinikum Leipzig
,
J. Thiery
1   Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik, Universitätsklinikum Leipzig
› Author Affiliations
Further Information

Publication History

Eingereicht am:05 July 2011

angenommen am:20 July 2011

Publication Date:
31 January 2018 (online)

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Zusammenfassung

Mit der Einführung der Tandem-Massenspektrometrie (MS/MS) für die Untersuchung von Aminosäuren und Acylcarnitinen im Rahmen des Neugeborenenscreenings (NGS) war es erstmals möglich, mit einem analytischen Test eine Vielzahl angeborener Stoffwechselstörungen zu erkennen. Aktuelle Entwicklungen auf dem Gebiet des NGS mit MS/MS liegen im „second-tier testing“, der Durchführung einer spezifischen tandemmassenspektrometrischen Folgediagnostik bei positivem Screeningergebnis aus der gleichen Filterpapierkarte (z. B. bei Ahornsiruperkrankung, Propion -azidurie, Adrenogenitales Syndrom). Daneben stehen nach der Entwicklung effektiver Therapiemöglichkeiten von einigen lysosomalen Speichererkrankungen tandemmassenspektrometrische Analysenverfahren für das Neugeborenenscreening aus Trockenblut zur Verfügung, die weltweit in verschiedenen Screeningprorgammen getestet werden. Im folgenden Beitrag werden neue analytische Konzepte auf Basis der Tandem-Massenspektrometrie für die Analytik aus Trockenblut und ihr Potenzial für das Neugeborenenscreening vorgestellt und diskutiert.

Summary

The introduction of tandem mass spectrometry in newborn screening programs enabled the screening of a number of inborn errors of metabolism within one single dried blood analysis. Recent developments in this field are mainly addressed to second-tier testings (e. g. for maple syrup urine disease, propionic aciduria, adrenogenital syndrome). In case of positive screening results a second mass spectrometric assay is applied using dried blood from the original filter paper card. The additional analysis often includes a chromatographic separation of other more specific disease-related markers. Main advantages of second-tier tests are the reduction of the false-postive results. The screening of lysosomal storage diseases by application of tandem mass spectrometry is another challenging development in the field of newborn screening. In this review new analytical concepts of LC-MS/MS for second-tier testing and the potential for screening of lysosomal storage will be discussed.

Schlüsselwörter

Neugeborenenscreening - second-tier testing - lysosomale Speichererkankungen - Tandem-Massenspektrometrie

Keywords

Newborn screening - second-tier tests - lysosomal storage diseases - tandem mass spectrometry
 

  • Literatur

  • 1 Chace DH. Mass spectrometry in newborn and metabolic screening: Historical perspective and future directions. J Mass Spectrom 2009; 44: 163-170.
    CrossrefPubMedGoogle Scholar
  • 2 Schulze A, Lindner M, Kohlmuller D. et al Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: Results, outcome, and implications. Pediatrics 2003; 111: 1399-1406.
    CrossrefPubMedGoogle Scholar
  • 3 Nennstiel-Ratzel U. et al Qualität des Neugeborenenscreenings nach Einführung der nationalen Screeningrichtlinien in Deutschland. Kinder und Jugendmedizin 2009; 2: 88-92.
    Google Scholar
  • 4 la Marca G, Malvagia S, Pasquini E. et al Rapid 2ndtier test for measurement of 3-oh-propionic and methylmalonic acids on dried blood spots: Reducing the false-positive rate for propionylcarnitine during expanded newborn screening by liquid chromatography-tandem mass spectrometry. Clin Chem 2007; 53: 1364-1369.
    CrossrefPubMedGoogle Scholar
  • 5 Turgeon CT, Magera MJ, Cuthbert CD. et al Determination of total homocysteine, methylmalonic acid, and 2-methylcitric acid in dried blood spots by tandem mass spectrometry. Clin Chem 2010; 56: 1686-1695.
    CrossrefPubMedGoogle Scholar
  • 6 Tortorelli S, Turgeon CT, Lim JS, Baumgart S. Day-Salvatore DL, Abdenur J. et al Two-tier approach to the newborn screening of methylenetetrahydrofolate reductase deficiency and other remethylation disorders with tandem mass spectrometry. J Pediatr 2010; 157: 271-275.
    CrossrefPubMedGoogle Scholar
  • 7 Abdenur JE, Chamoles NA, Guinle AE. et al Diagnosis of isovaleric acidaemia by tandem mass spectrometry: False positive result due to pivaloylcarnitine in a newborn screening programme. J Inherit Metab Dis 1998; 21: 624-630.
    CrossrefPubMedGoogle Scholar
  • 8 Rashed MS, Ozand PT, Bucknall MP, Little D. Diagnosis of inborn errors of metabolism from blood spots by acylcarnitines and amino acids profiling using automated electrospray tandem mass spectrometry. Pediatr Res 1995; 38: 324-331.
    CrossrefPubMedGoogle Scholar
  • 9 Chace DH, Kalas TA, Naylor EW. The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. Annu Rev Genomics Hum Genet 2002; 3: 17-45.
    CrossrefPubMedGoogle Scholar
  • 10 Forni S, Fu X, Palmer SE, Sweetman L. Rapid determination of c4-acylcarnitine and c5-acylcarnitine isomers in plasma and dried blood spots by uplcms/ ms as a second tier test following flow-injection ms/ms acylcarnitine profile analysis. Mol Genet Metab 2010; 101: 25-32.
    CrossrefPubMedGoogle Scholar
  • 11 Shigematsu Y, Hata I, Tajima G. Useful second-tier tests in expanded newborn screening of isovaleric acidemia and methylmalonic aciduria. J Inherit Metab Dis 2010; 33: S283-288.
    PubMedGoogle Scholar
  • 12 Matern D, Tortorelli S, Oglesbee D. et al Reduction of the false-positive rate in newborn screening by implementation of ms/ms-based second-tier tests: The mayo clinic experience (2004-2007). J Inherit Metab Dis 2007; 30: 585-592.
    CrossrefPubMedGoogle Scholar
  • 13 van Maldegem BT, Wanders RJ, Wijburg FA. Clinical aspects of short-chain acyl-coa dehydrogenase deficiency. J Inherit Metab Dis 2010; 33: 507-511.
    PubMedGoogle Scholar
  • 14 Janzen N, Sander S, Terhardt M. et al Fast and direct quantification of adrenal steroids by tandem mass spectrometry in serum and dried blood spots. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 861: 117-122.
    CrossrefPubMedGoogle Scholar
  • 15 Janzen N, Peter M, Sander S. et al Newborn screening for congenital adrenal hyperplasia: Additional steroid profile using liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 2007; 92: 2581-2589.
    CrossrefPubMedGoogle Scholar
  • 16 Minutti CZ, Lacey JM, Magera MJ. et al Steroid profiling by tandem mass spectrometry improves the positive predictive value of newborn screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 2004; 89: 3687-3693.
    CrossrefPubMedGoogle Scholar
  • 17 Schwarz E, Liu A, Randall H. et al Use of steroid profiling by uplc-ms/ms as a second tier test in newborn screening for congenital adrenal hyperplasia: The utah experience. Pediatr Res 2009; 66: 230-235.
    CrossrefPubMedGoogle Scholar
  • 18 Jensen UG, Brandt NJ, Christensen E. et al Neonatal screening for galactosemia by quantitative analysis of hexose monophosphates using tandem mass spectrometry: A retrospective study. Clin Chem 2001; 47: 1364-1372.
    PubMedGoogle Scholar
  • 19 Li Y, Ptolemy AS, Harmonay L. et al Ultra fast and sensitive liquid chromatography tandem mass spectrometry based assay for galactose-1-phosphate uridylyltransferase and galactokinase deficiencies. Mol Genet Metab 2011; 102: 33-40.
    CrossrefPubMedGoogle Scholar
  • 20 Ko DH, Jun SH, Park KU. et al Newborn screening for galactosemia by a second-tier multiplex enzyme assay using uplc-ms/ms in dried blood spots. J Inherit Metab Dis 2011; 34: 409-414.
    CrossrefPubMedGoogle Scholar
  • 21 Schulze A, Frommhold D, Hoffmann GF, Mayatepek E. Spectrophotometric microassay for deltaaminolevulinate dehydratase in dried-blood spots as confirmation for hereditary tyrosinemia type i. Clin Chem 2001; 47: 1424-1429.
    PubMedGoogle Scholar
  • 22 Weigel JF, Janzen N, Pfaffle RW. et al Tandem mass spectrometric determination of succinylacetone in dried blood spots enables presymptomatic detection in a case of hepatorenal tyrosinaemia. J Inherit Metab Dis 2007; 30: 610
    CrossrefPubMedGoogle Scholar
  • 23 Dhillon KS, Bhandal AS, Aznar CP. et al Improved tandem mass spectrometry (ms/ms) derivatized method for the detection of tyrosinemia type i, amino acids and acylcarnitine disorders using a single extraction process. Clin Chim Acta 2011; 412: 873-879.
    CrossrefPubMedGoogle Scholar
  • 24 Chace DH, Lim T, Hansen CR. et al Improved ms/ ms analysis of succinylacetone extracted from dried blood spots when combined with amino acids and acylcarnitine butyl esters. Clin Chim Acta 2009; 407: 6-9.
    CrossrefPubMedGoogle Scholar
  • 25 Morrissey MA, Sunny S, Fahim A. et al Newborn screening for tyr-i: Two years' experience of the new york state program. Mol Genet Metab 2011; 103: 191-192.
    CrossrefPubMedGoogle Scholar
  • 26 Lehotay DC, Hall P, Lepage J. et al Lc-ms/ms progress in newborn screening. Clin Biochem 2011; 44: 21-31.
    CrossrefPubMedGoogle Scholar
  • 27 Fletcher JM. Screening for lysosomal storage disorders -a clinical perspective. J Inherit Metab Dis 2006; 29: 405-408.
    CrossrefPubMedGoogle Scholar
  • 28 Nakamura K, Hattori K, Endo F. Newborn screening for lysosomal storage disorders. Am J Med Genet C Semin Med Genet 2011; 157: 63-71.
    CrossrefPubMedGoogle Scholar
  • 29 Matern D. Newborn screening for lysosomal storage disorders. Acta Paediatr Suppl 2008; 97: 33-37.
    CrossrefPubMedGoogle Scholar
  • 30 Khaliq T, Sadilek M, Scott CR. et al Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: Application to screening newborns for mucopolysaccharidosis iva. Clin Chem 2011; 57: 128-131.
    CrossrefPubMedGoogle Scholar
  • 31 Li Y, Scott CR, Chamoles NA. et al Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening. Clin Chem 2004; 50: 1785-1796.
    CrossrefPubMedGoogle Scholar
  • 32 Wang D, Wood T, Sadilek M. et al Tandem mass spectrometry for the direct assay of enzymes in dried blood spots: Application to newborn screening for mucopolysaccharidosis ii (hunter disease). Clin Chem 2007; 53: 137-140.
    PubMedGoogle Scholar
  • 33 Gelb MH, Turecek F, Scott CR, Chamoles NA. Direct multiplex assay of enzymes in dried blood spots by tandem mass spectrometry for the newborn screening of lysosomal storage disorders. J Inherit Metab Dis 2006; 29: 397-404.
    CrossrefPubMedGoogle Scholar
  • 34 Duffey TA, Bellamy G, Elliott S. et al A tandem mass spectrometry triplex assay for the detection of fabry, pompe, and mucopolysaccharidosis-i (hurler). Clin Chem 2010; 56: 1854-1861.
    CrossrefPubMedGoogle Scholar
  • 35 Duffey TA, Sadilek M, Scott CR. et al Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: Application to screening newborns for mucopolysaccharidosis vi (maroteaux-lamy syndrome). Anal Chem 2010; 82: 9587-9591.
    CrossrefPubMedGoogle Scholar
  • 36 Dajnoki A, Fekete G, Keutzer J. et al Newborn screening for fabry disease by measuring gla activity using tandem mass spectrometry. Clin Chim Acta 2010; 411: 1428-1431.
    CrossrefPubMedGoogle Scholar
  • 37 Kasper DC, Herman J, De Jesus VR. et al The application of multiplexed, multi-dimensional ultra-high-performance liquid chromatography/tandem mass spectrometry to the high-throughput screening of lysosomal storage disorders in newborn dried bloodspots. Rapid Commun Mass Spectrom 2010; 24: 986-994.
    CrossrefPubMedGoogle Scholar
  • 38 Duffner PK, Caggana M, Orsini JJ. et al Newborn screening for krabbe disease: The new york state model. Pediatr Neurol 2009; 40: 245-52. discussion 53-55
    CrossrefPubMedGoogle Scholar
  • 39 Marsden D, Levy H. Newborn screening of lysosomal storage disorders. Clin Chem 2010; 56: 1071-1079.
    CrossrefPubMedGoogle Scholar
  • 40 la Marca G, Casetta B, Malvagia S. et al New strategy for the screening of lysosomal storage disorders: The use of the online trapping-and-cleanup liquid chromatography/mass spectrometry. Anal Chem 2009; 81: 6113-6121.
    CrossrefPubMedGoogle Scholar
  • 41 Blanchard S, Sadilek M, Scott CR. et al Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: Application to screening newborns for mucopolysaccharidosis i. Clin Chem 2008; 54: 2067-2070.
    CrossrefPubMedGoogle Scholar