Newborn screening with tandem mass spectrometry: 12 months' experience in NSW Australia

TLDR

Since 1998, the NSW Newborn Screening Program has used electrospray tandem mass spectrometry to analyze samples from approximately 95,000 babies per year for selected amino acids and acylcarnitines. The program employs a software rules editor that interprets MS/MS ratios using external standard curves, uploads the numerical results to a database that automatically triggers analyte‑specific follow‑up cascades, and establishes cut‑off levels from population and retrospective data. In 137,120 consecutive newborns screened, the program identified 17 phenylketonuria cases and a spectrum of other metabolic disorders, demonstrating excellent specificity and sensitivity for detecting at least 40 rare inborn errors of metabolism.

Abstract

Since 1998, the NSW Newborn Screening Program has used electrospray tandem mass spectrometry (MS/MS) to analyse samples from all babies born in NSW and the ACT (approximately 95000 per year) for selected amino acids and acylcarnitines. The software rules editor initially interprets all results where ratio of analyte to internal standard is modified by input from the external standard curves per analyte. The numerical results are then downloaded to the NSW Newborn Screening database, which provides automatic, analyte specific follow-up test cascade. We have analysed samples from 137 120 consecutive newborns received by the program, requested repeat samples from 122 babies, and found abnormal levels in 17 babies with phenylketonuria, 1 tetrahydrobiopterin deficiency, 3 hyperphenylalaninaemia, 1 maple syrup urine disease, 1 tyrosinaemia type II, 1 congenital lactic acidosis, 2 medium-chain acyl CoA dehydrogenase deficiency, 1 short-chain acyl CoA dehydrogenase deficiency, 1 beta-ketothiolase deficiency, 2 vitamin B12 deficient babies of vegan mothers and 1 glutaric aciduria type I. Using population data plus that obtained from retrospective samples with proven disorders we have established cut-off levels for each analyte tested. This coupled with the ability of the database to provide ratios of various analytes gives excellent screening specificity and sensitivity for the detection of at least 40 rare inborn errors of metabolism.