Newborn screening for isovaleric acidemia using tandem mass spectrometry: data from 1.6 million newborns
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Newborn screening for isovaleric acidemia using tandem mass spectrometry: data from 1.6 million newborns. / Ensenauer, Regina; Fingerhut, Ralph; Maier, Esther M; Polanetz, Roman; Olgemöller, Bernhard; Röschinger, Wulf; Muntau, Ania C.
in: CLIN CHEM, Jahrgang 57, Nr. 4, 04.2011, S. 623-6.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Newborn screening for isovaleric acidemia using tandem mass spectrometry: data from 1.6 million newborns
AU - Ensenauer, Regina
AU - Fingerhut, Ralph
AU - Maier, Esther M
AU - Polanetz, Roman
AU - Olgemöller, Bernhard
AU - Röschinger, Wulf
AU - Muntau, Ania C
PY - 2011/4
Y1 - 2011/4
N2 - BACKGROUND: Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) has been used in the Bavarian newborn screening (NBS) program since 1999. The use of ESI-MS/MS has led to the inclusion of isovaleric acidemia (IVA) into NBS. We retrospectively evaluated data on more than 1.6 million newborns screened during 9.5 years.METHODS: Acylcarnitines from whole blood spotted on filter paper were converted to their corresponding butyl esters, and the samples were analyzed by use of ESI-MS/MS with stable isotope labeled internal standards.RESULTS: A total of 24 individuals with IVA were detected by use of a multiparametric threshold criteria panel including isovalerylcarnitine (C5) and the ratios of C5 to octanoyl-, butyryl-, and propionylcarnitine. A cutoff set at the 99.99th percentile for isolated C5 or at the 99th percentile for C5 plus at least 2 ratios resulted in a positive predictive value for IVA screening of 7.0% and an overall recall rate of 0.024%. Adjusted reference ranges for age and birth weight were applied, and the incidence of IVA in the study population was calculated to be 1 in 67,000. Missed cases were not brought to our attention. IVA was also detectable in cord blood and early postnatal blood samples.CONCLUSIONS: IVA can be reliably detected in NBS through acylcarnitine analysis in dried blood spots by using multiparametric threshold criteria. Further improvement (positive predictive value 13.0%, recall rate 0.01%) can be achieved by using more stringent recall criteria. In view of the potentially life-threatening natural course of IVA in early life, presymptomatic diagnosis may thus prevent mortality and morbidity.
AB - BACKGROUND: Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) has been used in the Bavarian newborn screening (NBS) program since 1999. The use of ESI-MS/MS has led to the inclusion of isovaleric acidemia (IVA) into NBS. We retrospectively evaluated data on more than 1.6 million newborns screened during 9.5 years.METHODS: Acylcarnitines from whole blood spotted on filter paper were converted to their corresponding butyl esters, and the samples were analyzed by use of ESI-MS/MS with stable isotope labeled internal standards.RESULTS: A total of 24 individuals with IVA were detected by use of a multiparametric threshold criteria panel including isovalerylcarnitine (C5) and the ratios of C5 to octanoyl-, butyryl-, and propionylcarnitine. A cutoff set at the 99.99th percentile for isolated C5 or at the 99th percentile for C5 plus at least 2 ratios resulted in a positive predictive value for IVA screening of 7.0% and an overall recall rate of 0.024%. Adjusted reference ranges for age and birth weight were applied, and the incidence of IVA in the study population was calculated to be 1 in 67,000. Missed cases were not brought to our attention. IVA was also detectable in cord blood and early postnatal blood samples.CONCLUSIONS: IVA can be reliably detected in NBS through acylcarnitine analysis in dried blood spots by using multiparametric threshold criteria. Further improvement (positive predictive value 13.0%, recall rate 0.01%) can be achieved by using more stringent recall criteria. In view of the potentially life-threatening natural course of IVA in early life, presymptomatic diagnosis may thus prevent mortality and morbidity.
KW - Humans
KW - Infant, Newborn
KW - Neonatal Screening
KW - Pentanoic Acids
KW - Spectrometry, Mass, Electrospray Ionization
KW - Tandem Mass Spectrometry
U2 - 10.1373/clinchem.2010.151134
DO - 10.1373/clinchem.2010.151134
M3 - SCORING: Journal article
C2 - 21335445
VL - 57
SP - 623
EP - 626
JO - CLIN CHEM
JF - CLIN CHEM
SN - 0009-9147
IS - 4
ER -