BACKGROUND: The expansion of newborn screening programs has increased the number of newborns diagnosed with inborn errors of metabolism in the presymptomatic phase, but it has also increased the number of costly, stress-producing false-positive results. Because propionylcarnitine (C3) is one of the analytes most frequently responsible for false-positive results, we aimed to develop a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to identify free methylmalonic (MMA) and 3-OH propionic (3OH-PA) acids in blood spots. METHODS: We studied newborn screening spots from 250 healthy controls; 124 from infants with abnormal C3, of whom only 5 (4%) were truly affected; 124 from infants with altered isolated methylmalonylcarnitine; and 4 from clinically diagnosed patients. Whole blood was eluted from a 3.2-mm dried blood spot by a CH(3)CN/H(2)O 7:3 and 5 mL/L formic. This extract was injected into a LC-MS/MS equipped with pneumatically assisted electrospray without derivatization. Total analysis time was 5 min per sample. RESULTS: The assays were linear up to 3300 nmol/L for both metabolites. Intra- and interassay imprecision data were 3.6%-8% and 3.1%-6%, respectively, for MMA and 5.2%-20% and 3.6%-17% for 3OH-PA. Limit of detection and limit of quantitation were 1.95 and 4.2 micromol/L, respectively, for MMA and 8 and 10 micromol/L for 3OH-PA. The recoveries were 92.9%-106.1%. No deterioration was noted on the columns after 500 chromatographic runs. If the new method had been used as a 2nd-tier test for the 124 samples, only the 5 true positives would have been recalled for additional samples, and the positive predictive value would have been 100%. CONCLUSIONS: This method has the potential to markedly reduce false-positive results and the associated costs and anxiety. It may also be suitable for diagnosing and routinely monitoring blood spots for methylmalonic aciduria and propionic acidemia.
BACKGROUND: The expansion of newborn screening programs has increased the number of newborns diagnosed with inborn errors of metabolism in the presymptomatic phase, but it has also increased the number of costly, stress-producing false-positive results. Because propionylcarnitine (C3) is one of the analytes most frequently responsible for false-positive results, we aimed to develop a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to identify free methylmalonic (MMA) and 3-OH propionic (3OH-PA) acids in blood spots. METHODS: We studied newborn screening spots from 250 healthy controls; 124 from infants with abnormal C3, of whom only 5 (4%) were truly affected; 124 from infants with altered isolated methylmalonylcarnitine; and 4 from clinically diagnosed patients. Whole blood was eluted from a 3.2-mm dried blood spot by a CH(3)CN/H(2)O 7:3 and 5 mL/L formic. This extract was injected into a LC-MS/MS equipped with pneumatically assisted electrospray without derivatization. Total analysis time was 5 min per sample. RESULTS: The assays were linear up to 3300 nmol/L for both metabolites. Intra- and interassay imprecision data were 3.6%-8% and 3.1%-6%, respectively, for MMA and 5.2%-20% and 3.6%-17% for 3OH-PA. Limit of detection and limit of quantitation were 1.95 and 4.2 micromol/L, respectively, for MMA and 8 and 10 micromol/L for 3OH-PA. The recoveries were 92.9%-106.1%. No deterioration was noted on the columns after 500 chromatographic runs. If the new method had been used as a 2nd-tier test for the 124 samples, only the 5 true positives would have been recalled for additional samples, and the positive predictive value would have been 100%. CONCLUSIONS: This method has the potential to markedly reduce false-positive results and the associated costs and anxiety. It may also be suitable for diagnosing and routinely monitoring blood spots for methylmalonic aciduria and propionic acidemia.
Authors: Edward S Y Wong; Chantelle McIntyre; Heidi L Peters; Enzo Ranieri; Donald S Anson; Janice M Fletcher Journal: Hum Gene Ther Date: 2014-04-02 Impact factor: 5.695
Authors: Gwendolyn Gramer; Junmin Fang-Hoffmann; Patrik Feyh; Glynis Klinke; Peter Monostori; Jürgen G Okun; Georg F Hoffmann Journal: World J Pediatr Date: 2018-06-15 Impact factor: 2.764
Authors: Gerarda Cappuccio; Paldeep S Atwal; Taraka R Donti; Kiki Ugarte; Nadia Merchant; William J Craigen; V Reid Sutton; Sarah H Elsea Journal: JIMD Rep Date: 2016-11-30
Authors: David C Kasper; Rene Ratschmann; Thomas F Metz; Thomas P Mechtler; Dorothea Möslinger; Vassiliki Konstantopoulou; Chike B Item; Arnold Pollak; Kurt R Herkner Journal: Wien Klin Wochenschr Date: 2010-10-15 Impact factor: 1.704
Authors: Sabrina Malvagia; Christopher A Haynes; Laura Grisotto; Daniela Ombrone; Silvia Funghini; Elisa Moretti; Kathleen S McGreevy; Annibale Biggeri; Renzo Guerrini; Raquel Yahyaoui; Uttam Garg; Mary Seeterlin; Donald Chace; Victor R De Jesus; Giancarlo la Marca Journal: Clin Chim Acta Date: 2015-09-11 Impact factor: 3.786