Abstract
Since its inception six decades ago, newborn screening has been lauded as a highly successful and cost-effective public health program by identifying disorders at the presymptomatic stage, enabling early disease-modifying intervention that otherwise invariably leads to death or permanent damage if treated at the symptomatic stage. The advent of multiplex high-throughput assays involving chromatography coupled with mass spectroscopy enabled the analysis of multiple disorders in a single run, vastly increasing the repertoire of screened disorders while keeping the cost nearly the same. Industrialized countries provide unified screening for more than 50 conditions, compared to about a dozen, a mere decade ago. Inevitably, we now screen, in essence, more than we know how to treat. Nonetheless, as a constant flow of new therapies breaks ground, providing accurate diagnostic data is vital for patient outcomes. Breaking the diagnostic barrier can mean new research, new drugs, and ultimately increased survival. In this chapter, we overview the concept of untargeted metabolomics as applied to newborn screening, how it fares compared to the well-standardized tests of the targeted screening, and its ability to screen for more disorders that are currently “unscreenable.”
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Glossary
- Dried blood spot (DBS)
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A method of whole blood sample collection, in which a small amount of fresh blood is blotted onto an absorbent filter paper, followed by drying. This method provides a convenient storage and shipment platform and is widely used for newborn screening. Typically, a small punch from the DBS paper is eluted with phosphate-buffered saline, availing the sample for testing.
- Multiplex assay
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An assay measuring simultaneously multiple analytes in a single testing. These tests are becoming more popular in the metabolic sciences where several similar analytes are tested for alterations from the normal range, e.g., urine polyols for evaluation of the pentose phosphate pathway, urine glycosaminoglycans for the diagnosis of mucopolysaccharidoses, or carbohydrate moieties for congenital disorders of glycosylation.
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Manor, J., Elsea, S.H. (2023). Untargeted Metabolomics in Newborn Screening. In: Abdel Rahman, A.M. (eds) Clinical Metabolomics Applications in Genetic Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-99-5162-8_5
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DOI: https://doi.org/10.1007/978-981-99-5162-8_5
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