Tandem mass spectrometry: the tool of choice for diagnosing inborn errors of metabolism?

Abstract

The early diagnosis of inborn errors of metabolism (IEM) by laboratory-based mass screening is a prime example of preventive medicine. However, several factors restrict the range of IEM that can be screened for, and the numbers of people to whom it can be made available. Mass screening in the United Kingdom is limited primarily to that for phenylketonuria and congenital hypothyroidism. Ideally, extension of mass screening of neonates for additional clinically significant IEM is a desirable strategy. Tandem mass spectrometry (TMS) is a powerful and effective diagnostic technique and has been proposed as a means to realise this aim. Its main advantages are improved accuracy, sensitivity and specificity over existing methods, and its suitability for cost-effective multidisease IEM mass screening. The evolution, principles and applications of TMS are described, and the practical and clinical implications of extending diagnostic services for IEM using TMS are discussed.

Keywords:

• Metabolism, inborn errors
• Spectrum analysis, tandem mass