Newborn Screening by Tandem Mass Spectrometry

Abstract

Major expansion of newborn screening for inherited metabolic disorders is taking place across the US and around the world as newer analytical technology is applied. Historically, each disorder to be screened required a separate test with associated costs and requirement for a portion of the dried-blood-spot specimen from a heel stick. This limitation of the existing tests was partially responsible for the limitation of mandated newborn screening in the US to a small number of disorders (usually three to seven, depending on the state). The technique of tandem mass spectrometric (MS) analysis of dried-blood spots was first proposed for newborn screening in 1990 by Millington et al. (1). Using ionization techniques of fast atom bombardment or liquid secondary ionization with tandem MS, they simultaneously determined a large number of acylcarnitines as an acylcarnitine profile. This allowed newborn screening for numerous inherited fatty acid oxidation and organic acid disorders by a single procedure. Tandem MS was extended to amino acids, including phenylalanine, the screening target for detection of the phenylketonuria (PKU) test (2)(3)(4), and to other disorders, with several such tests described in these pages during the last 8 years (3)(5)(6)(7)(8)(9). The development and application of electrospray ionization (ESI) tandem MS with its ability to be automated made high-volume tandem MS screening for amino acid, organic acid, and fatty acid metabolic disorders practical by the mid-1990s (10)(11)(12). Automated ESI tandem MS newborn screening of amino acids …