Newborn screening for hepatorenal tyrosinemia-I by tandem mass spectrometry using pooled samples: A four-year summary by the New England newborn screening program

ObjectiveThe objective of this study is to develop an isotope dilution liquid chromatography tandem mass spectrometry assay to screen for hepatorenal tyrosinemia (HT) from newborn filter paper samples using pooled extracts to increase high throughput screening.Design and methodsSuccinylacetone (SUAC), the marker for HT, was extracted from dried blood spots with the formation of the hydrazone derivative of SUAC; up to eight sample extracts were pooled and the SUAC-derivative was analyzed by mass spectrometry methods with an injection-to-injection time of one minute. If any pooled sample extract screened positive, then the samples comprising the pooled sample were assayed individually.ResultsTwo newborn infants were identified with high levels of SUAC (7 & 23 μM) and later confirmed to have HT. Three older children whose initial filter paper samples were taken at 195 days to 614 days of age with elevated SUAC (range 4.9–5 μM) were identified; one of the three had clinical signs of HT and was placed on treatment (diagnosis of the other two are unavailable).ConclusionMS/MS analysis of pooled dried blood sample extracts permits sensitive, reduced instrumental analytical time and increase high throughput screening for HT.

► Screening for Tyrosinemia-I using the hydrazone derivative of succinylacetone.
► Pooled extracts from newborn dried blood spots can be used to screen for Tyrosinemia.
► High throughput screening for Tyrosinemia using tandem mass spectrometry.