Diagnosis of inborn errors of metabolism by tandem mass spectrometry.

Technological advances are revolutionizing the way in which we can diagnose and screen whole populations for inborn errors of metabolism. These advances are also necessitating a reevaluation of the spectrum of metabolic disorders included in newborn screening program. The initial concept for inclusion into a screening program was based upon a number of factors, including the use of one test on one sample for a single disease. Early assay capabilities limited the number of tests that a screening center could perform on the filter paper blood spot sample collected shortly after birth. As technology and assay sensitivity improved, more tests could be performed on a dried blood spot sample, expanding the laboratory’s ability to screen for more than one disorder in the newborn period. In the last decade, the evolution of tandem mass spectrometry has improved our diagnostic capabilities further. We can now readily detect multiple diseases on a single sample, using a single analytical procedure. This review will highlight historical aspects of newborn screening for inborn errors of metabolism, describe state-of-the-art screening practices and focus upon possible future trends for this important area of laboratory testing.