Development of a Universal Second-Tier Newborn Screening LC–MS/MS Method for Amino Acids, Lysophosphatidylcholines, and Organic Acids

Kilgore, Matthew B.; Platis, Dimitrios; Lim, Timothy; Isenberg, Samantha; Pickens, C. Austin; Cuthbert, Carla; Petritis, Konstantinos

doi:10.1021/acs.analchem.2c03098

DOE OSTI · 2471246

Development of a Universal Second-Tier Newborn Screening LC–MS/MS Method for Amino Acids, Lysophosphatidylcholines, and Organic Acids

Kilgore, Matthew B.·Platis, Dimitrios·Lim, Timothy·Isenberg, Samantha·Pickens, C. Austin·Cuthbert, Carla·Petritis, Konstantinos

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Abstract

First-tier MS-based newborn screening by flow injection analysis can have high presumptive positive rates, often due to isomeric/isobaric compounds or poor biomarker specificity. These presumptive positive samples can be analyzed by second-tier screening assays employing separations such as liquid chromatography–mass spectrometry (LC–MS/MS), which increases test specificity and drastically reduces false positive referrals. The ability to screen for multiple disorders in a single multiplexed test simplifies workflows and maximizes public health laboratories’ resources. In this study, we developed and validated a highly multiplexed second-tier method for dried blood spots using a hydrophilic interaction liquid chromatography (HILIC) column coupled to an MS/MS system. The LC–MS/MS method was capable of simultaneously detecting second-tier biomarkers for maple syrup urine disease, homocystinuria, methylmalonic acidemia, propionic acidemia, glutaric acidemia type 1, glutaric acidemia type 2, guanidinoacetate methyltransferase deficiency, short-chain acyl-CoA dehydrogenase deficiency, adrenoleukodystrophy, and Pompe disease.

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Kilgore, Matthew B., Platis, Dimitrios, Lim, Timothy, Isenberg, Samantha, Pickens, C. Austin, Cuthbert, Carla, Petritis, Konstantinos. 2023-02-01. Development of a Universal Second-Tier Newborn Screening LC–MS/MS Method for Amino Acids, Lysophosphatidylcholines, and Organic Acids. https://doi.org/10.1021/acs.analchem.2c03098

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