Newborn Screening by Tandem Mass Spectrometry: A New Era

Soon after Guthrie (1) expanded newborn screening by adding galactosemia, maple syrup urine disease (MSUD), and homocystinuria to the original screening for phenylketonuria (PKU), he realized that screening would be more efficient and comprehensive if a single assay could be used to detect several disorders rather than the system of a separate bacterial assay for each disorder that he had developed. He tried many ways to make such a single assay–using multiple inhibitors and different strains of bacteria–but nothing worked, so he abandoned the idea. Others had the same idea but used chromatography rather than bacterial assays (2)(3). Unfortunately, paper chromatography was insufficiently sensitive for screening newborn blood within the first days of life when the specimen is collected. To compensate for this shortcoming and to further expand the coverage of disorders, paper or thin-layer chromatography has been used for screening newborn urine (4). But here again, chromatography has had substantial disadvantages. First, an additional specimen is required because urine cannot replace blood in detecting either PKU or congenital hypothyroidism, the two indispensable disorders in screening. Second, the urine specimen must be collected by a parent or physician after nursery discharge, introducing a logistical problem. Third, urine varies widely in concentration, producing many false-positive results in the more highly concentrated specimens. This leads to otherwise unnecessary, anxiety-provoking requests for repeat specimens. Conversely, false-negative findings may result from dilute specimens. Finally, many of the disorders identified in urine, such as histidinemia, iminoglycinuria, and Hartnup disorder, are benign (4). Consequently, newborn urine screening based on chromatography has been discontinued in two of the three places in which was introduced, Australia (5) and Massachusetts, remaining only in Quebec (6). Thus, screening programs continue to rely on the “one test-one …