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.
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.
Authors: María L Couce; Luís Aldamiz-Echevarría; María A Bueno; Patricia Barros; Amaya Belanger-Quintana; Javier Blasco; María-Teresa García-Silva; Ana M Márquez-Armenteros; Isidro Vitoria; Inmaculada Vives; Rosa Navarrete; Ana Fernández-Marmiesse; Belén Pérez; Celia Pérez-Cerdá Journal: J Hum Genet Date: 2016-12-01 Impact factor: 3.172
Authors: Olivia M D'Annibale; Erik A Koppes; Ahmad N Alodaib; Catherine Kochersperger; Anuradha Karunanidhi; Al-Walid Mohsen; Jerry Vockley Journal: Mol Genet Metab Date: 2021-08-30 Impact factor: 4.204
Authors: Sarah C Grünert; Udo Wendel; Martin Lindner; Michael Leichsenring; K Otfried Schwab; Jerry Vockley; Willy Lehnert; Regina Ensenauer Journal: Orphanet J Rare Dis Date: 2012-01-25 Impact factor: 4.123