Liquid Chromatography-Tandem Mass Spectrometry in Newborn Screening Laboratories

Michael H Gelb¹, Khaja Basheeruddin², Alberto Burlina³, Hsiao-Jan Chen⁴, Yin-Hsiu Chien⁵, George Dizikes⁶, Christine Dorley⁶, Roberto Giugliani⁷, Amy Hietala⁸, Xinying Hong¹, Shu-Min Kao⁴, Hamid Khaledi⁹, Tracy Klug¹⁰, Francyne Kubaski⁷, Hsuan-Chieh Liao¹¹, Monica Martin¹², Adrienne Manning¹³, Joseph Orsini¹², Yin Peng², Enzo Ranieri¹⁴, Andreas Rohrwasser¹⁵, Nicolas Szabo-Fresnais¹⁵, Coleman T Turgeon¹⁶, Frédérick M Vaz¹⁷, Li-Yun Wang¹⁸, Dietrich Matern¹⁶

Affiliations

¹ Departments of Chemistry and Biochemistry, University of Washington, Seattle, WA 98195, USA.
² Newborn Screening Laboratory, Illinois Department of Public Health, Chicago, IL 60612, USA.
³ Division of Inherited Metabolic Diseases, Reference Centre Expanded Newborn Screening, University Hospital Padova, 35128 Padova, Italy.
⁴ The Chinese Foundation of Health, Neonatal Screening Center, Taipei 110, Taiwan.
⁵ Department of Medical Genetics and Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
⁶ Tennessee Department of Health, Division of Laboratory Services, Knoxville, TN 37920, USA.
⁷ Department of Genetics UFRGS, Medical Genetics Service, HCPA, DASA and Casa dos Raros, Porto Alegre 91501970, Brazil.
⁸ Newborn Screening Laboratory, Minnesota Department of Health, St. Paul, MN 55164, USA.
⁹ GelbChem LLC, 4000 Mason Road, #300, Seattle, WA 98105, USA.
¹⁰ Missouri Department of Health and Senior Services, P.O. Box 570, Jefferson City, MO 65102, USA.
¹¹ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.
¹² Wadsworth Center, New York State Department of Health, Newborn Screening Program, David Axelrod Institute, 120 New Scotland Ave., Albany, NY 12201, USA.
¹³ Connecticut Department of Public Health, Katherine A. Kelley Public Health Laboratory, Rocky Hill, CT 06067, USA.
¹⁴ Genetics and Molecular Pathology, SA Pathology (WCH Site), Adelaide 5043, Australia.
¹⁵ Utah Department of Health and Human Services, Salt Lake City, UT 84129, USA.
¹⁶ Department of Laboratory Medicine and Pathology, Biochemical Genetics Laboratory, Mayo Clinic, Rochester, MN 55902, USA.
¹⁷ Laboratory Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
¹⁸ Taipei Institute of Pathology, Taipei 103, Taiwan.

PMID: 36547379
PMCID: PMC9781967
DOI: 10.3390/ijns8040062

Review

Liquid Chromatography-Tandem Mass Spectrometry in Newborn Screening Laboratories

Michael H Gelb et al. Int J Neonatal Screen. 2022.

. 2022 Nov 28;8(4):62.

doi: 10.3390/ijns8040062.

Authors

Affiliations

¹ Departments of Chemistry and Biochemistry, University of Washington, Seattle, WA 98195, USA.
² Newborn Screening Laboratory, Illinois Department of Public Health, Chicago, IL 60612, USA.
³ Division of Inherited Metabolic Diseases, Reference Centre Expanded Newborn Screening, University Hospital Padova, 35128 Padova, Italy.
⁴ The Chinese Foundation of Health, Neonatal Screening Center, Taipei 110, Taiwan.
⁵ Department of Medical Genetics and Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
⁶ Tennessee Department of Health, Division of Laboratory Services, Knoxville, TN 37920, USA.
⁷ Department of Genetics UFRGS, Medical Genetics Service, HCPA, DASA and Casa dos Raros, Porto Alegre 91501970, Brazil.
⁸ Newborn Screening Laboratory, Minnesota Department of Health, St. Paul, MN 55164, USA.
⁹ GelbChem LLC, 4000 Mason Road, #300, Seattle, WA 98105, USA.
¹⁰ Missouri Department of Health and Senior Services, P.O. Box 570, Jefferson City, MO 65102, USA.
¹¹ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.
¹² Wadsworth Center, New York State Department of Health, Newborn Screening Program, David Axelrod Institute, 120 New Scotland Ave., Albany, NY 12201, USA.
¹³ Connecticut Department of Public Health, Katherine A. Kelley Public Health Laboratory, Rocky Hill, CT 06067, USA.
¹⁴ Genetics and Molecular Pathology, SA Pathology (WCH Site), Adelaide 5043, Australia.
¹⁵ Utah Department of Health and Human Services, Salt Lake City, UT 84129, USA.
¹⁶ Department of Laboratory Medicine and Pathology, Biochemical Genetics Laboratory, Mayo Clinic, Rochester, MN 55902, USA.
¹⁷ Laboratory Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
¹⁸ Taipei Institute of Pathology, Taipei 103, Taiwan.

PMID: 36547379
PMCID: PMC9781967
DOI: 10.3390/ijns8040062

Abstract

Tandem mass spectrometry (MS/MS) is the most universal platform currently available for the analysis of enzymatic activities and biomarkers in dried blood spots (DBS) for applications in newborn screening (NBS). Among the MS/MS applications in NBS, the most common is flow-injection analysis (FIA-) MS/MS, where the sample is introduced as a bolus injection into the mass spectrometer without the prior fractionation of analytes. Liquid chromatography combined with MS/MS (LC-MS/MS) has been employed for second-tier tests to reduce the false-positive rate associated with several nonspecific screening markers, beginning two decades ago. More recently, LC-MS/MS has been applied to primary screening for new conditions for which FIA-MS/MS or other methods, including genomic screening, are not yet adequate. In addition to providing a list of the currently used LC-MS/MS-based assays for NBS, the authors share their experience regarding the maintenance requirements of LC-MS/MS vs. FIA-MS/MS systems. The consensus is that the maintenance of LC-MS/MS and FIA-MS/MS instrumentation is similar, and LC-MS/MS has the advantage of allowing for a larger number of diseases to be screened for in a multiplex, cost-effective fashion with a high throughput and an adequate turnaround time.

Keywords: dried blood spots; inborn errors of metabolism; liquid chromatography; newborn screening; reflex testing; tandem mass spectrometry.

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Conflict of interest statement

M.H. Gelb and H. Khaledi are co-founders of GelbChem, LLC.

References

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Liquid Chromatography-Tandem Mass Spectrometry in Newborn Screening Laboratories

Affiliations

Liquid Chromatography-Tandem Mass Spectrometry in Newborn Screening Laboratories

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous