Against this backdrop Wilcken et al compared the effectiveness screening for inborn errors of metabolism in all newborns with tandem mass spectrometry from 1998 to 2002 to conventional biochemical screening performed because of clinical suspicion from 1974 to 1998. The study population lived in New South Wales (Australia) and the Australian Capital Territory and totaled six million. Thirty-one disorders were selected for study. PKU and pterin disorders were excluded because effective screening by other methods had been in place for many years; also excluded were disorders known to be benign or of maternal origin.
The diagnosis rates were reported in four-year brackets, i.e., 1974-1978, 1978-1982 … 1998-2002, etc. During the six four-year periods preceding the implementation of tandem mass spectrometry screening, 22-34 cases were diagnosed per period giving rates from 6.6 to 9.0 cases per 100,000 births. Diagnoses were made at different ages depending on the age of clinical presentation. There were no trends toward increased overall rates of diagnosis between 1982 and 1998 even though some of the 31 disorders were first recognized during these periods.
Between 1998 and 2002, when all infants were tested between 48 and 72 hours after birth, 57 infants were diagnosed with one of the 31 inborn errors or 15.7 diagnoses per 100,000 births. Of these, 48 infants were diagnosed by screening, while six were diagnosed clinically before or at the same time as the screening result became available, usually within 24 hours of testing. Two patients, siblings with ornithine transcarbamylase deficiency born to a mother with known risk, did not undergo screening. Seven patients whose diagnoses were made later on clinical grounds had negative results on newborn screening.
Although results showed an increase in the rate of diagnosis following the introduction mass spectrometry screening in newborns, most of the increase could be accounted for by the diagnosis of medium-chain acyl-CoA dehydrogenase deficiency and to a lesser extent by the diagnosis of other disorders of fatty acid oxidation.
The authors calculated the cost of establishing a diagnosis. The incremental cost of the tandem mass spectrometry screening was $0.70 (USD) per newborn. The cost of confirmatory testing was $217 and the cost per relevant disorder detected was $3,939 if PKU was excluded or $2,519 if it was included. They concluded that their approach provides a rapid and inexpensive way to screen for a wide range of very rare metabolic diseases and that it identifies more cases than are diagnosed clinically. However they caution that it is not yet clear which patients identified through newborn screening would have become symptomatic if screening had not been performed.
Wilcken B et al. New Eng J Med 2003;348:2304-2312.
Editor’s Comment: This paper brings to the fore the debate over the extent to which tandem mass spectrometry technology should be used to screen for a growing number of inborn errors of metabolism. As noted in a recent article by Marshall,1 the debate pits parents and often physicians who advocate the application of this technology against ethicists with concerns over costs and public health officials with concerns over how the potentially large amount of genetic data will be managed. The Wilcken study demonstrates the successful implementation of the technology in a public health setting. It documents that the technology leads to an increased rate of diagnosis at low cost, especially for disorders of fatty acid oxidation, although acknowledges the possibility that some patients diagnosed as newborns may not have become symptomatic if screening had not been performed. Readers should note that metabolic screening by tandem mass spectrometry was highlighted by a recent lead article in GGH.2 This article explains how technology works, provides guidelines for its use and describes its successful application in North Carolina. Together, these articles provide support for advocates of wider use of tandem mass spectrometry for newborn screening.
References
1. Marshall E. Science 2001;294:2272-2274.
2. Millington D, Koeberl D. GGH 2003;19:32-38.
William A. Horton, MD