Enhanced metabolite profiling for newborn screening (2012)


Human Health


Newborn screening (NBS) programs represents one of the few proven strategies to prevent infant mortality and long-term disabilities associated with rare yet treatable genetic diseases. Early detection allows for prompt therapeutic intervention that improves clinical outcomes for infants. The recent advent of tandem mass spectrometry (MS/MS) has revolutionized NBS by enabling rapid metabolite profiling of dried blood spot samples collected via a heel prick of every newborn in Ontario. Despite the remarkable success of MS/MS technology, sample pretreatment currently limits the range of metabolites and classes of genetic diseases that can be reliably screened. This project, under Drs. Philip Britz-McKibbin (McMaster University) and Osama Aldirbashi (Newborn Screening Ontario, Children’s Hospital of Eastern Ontario), will develop a novel chemical reagent that permits efficient labeling of clinically relevant metabolites under mild/ambient conditions while potentially boosting sensitivity over two orders of magnitude. This is crucial for expanding NBS to encompass trace levels of metabolites that are difficult to analyze by MS/MS yet serve as primary biomarkers of various genetic disorders. To translate these findings into a marketable product for the clinical laboratory, the metabolomics team at McMaster University will optimize a chemical reagent kit which will be evaluated and validated at Newborn Screening Ontario in the Children’s Hospital of Eastern Ontario. This project will not only enhance the analytical performance of metabolite profiling by MS/MS for additional genetic diseases at minimal incremental costs, but also improve the efficacy of NBS programs by replacing classical biochemical assays that are prone to false-positives.