Rapid 2nd-tier 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.

Background: The expansion of newborn screening programs has increased the diagnosis of inborn errors of metabolism in the presymptomatic phase. However, it has also led to a significant increase in the number of false-positive results. This is costly for Public Health Resources and causes anxiety for parents. Methods: Since propionylcarnitine (C3) is one of the analytes most frequently responsible for false-positive results, we developed a rapid LC-MS/MS method that identifies free methylmalonic and 3-OH propionic acids in blood spots thus reducing false-positive rates due to C3 during expanded newborn screening programs. This method could also be suitable for diagnosing and routinely monitoring blood spots for methylmalonic aciduria and propionic acidemia. Analysis consists of chromatographic separation on a C6-Phenyl column of an extracted 3.2 mm dried blood spot and injection into a mass spectrometer. No derivatization is required. Total analysis time is 5 minutes per sample.