Perspectives on Next-Generation Newborn Screening

Kyoung-Jin Park; Jong-Won Kim

doi:10.3343/lmo.2015.5.4.169

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Park and Kim: Perspectives on Next-Generation Newborn Screening

Perspective

Diagnostic Genetics

Laboratory Medicine Online 2015; 5(4): 169-175.

Published online: 1 October 2015

DOI: https://doi.org/10.3343/lmo.2015.5.4.169

Perspectives on Next-Generation Newborn Screening

Kyoung-Jin Park, M.D.¹, Jong-Won Kim, M.D.^1,²

¹Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.

²Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Corresponding author: Jong-Won Kim. Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. Tel: +82-2-3410-2705, Fax: +82-2-3410-2719, kimjw@skku.edu

Received 29 January 2015 Revised 9 March 2015 Accepted 10 March 2015

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Newborn screening (NBS) has been effective for detecting asymptomatic newborns with inherited metabolic diseases and has facilitated early clinical intervention, which has resulted in significant decreases in the rates of morbidity and mortality caused by these diseases. The outcome of the NBS program heavily depends on technological advances. Since Dr. Robert Guthrie developed a bacterial inhibition assay to screen for metabolic diseases in the early 1960s, use of the NBS program has spread to many countries. Tandem mass spectrometry (TMS) was a second major technological breakthrough that has allowed screening to be extended to disorders of fatty acid and organic acid metabolism as well as to those of amino acid metabolism, and recently screening has also been expanded to include lysosomal storage diseases. TMS can detect multiple analytes rapidly and simultaneously and is currently applied to nearly 80% of the newborn population in Korea. Next-generation sequencing (NGS) technology could be another major breakthrough to improve the current NBS program. To integrate NGS into the NBS program, various considerations about its analytical validity, clinical validity, clinical utility, and ethical, legal, and social implications should be addressed on the basis of population screening. Here, the authors review population screening criteria, the current status of NBS, and recent advances in NGS. In addition, we discuss the practical and ethical issues, opportunities, and challenges regarding the implementation of NGS in NBS.

Keywords: Newborn screening (NBS), Inherited metabolic disease, Next generation sequencing (NGS), Tandem mass spectrometry (TMS)

Figures and Tables

Fig. 1

Types of newborn screening workflow. (A) Current newborn screening workflow. (B) Use of next-generation sequencing as a second-tier tests. (C) Use of next-generation sequencing as a main screening method.

Table 1

Comparison between current and next-generation newborn screening

	Current newborn screening			Next-generation newborn screening
	First-tier tests	Second-tier tests
	First-tier tests	Biochemical analysis	Molecular tests
Purpose	Screening	Screening and/or confirmatory	Confirmatory	Screening and/or confirmatory
Methods	immunoassay	Amino acid analysis	Targeted genotyping	Whole-exome sequencing
	Radioimmunoassay	Acylcarnitine analysis	Sanger sequencing	Whole-genome sequencing
	Tandem mass spectrometry	Organic acid analysis		Targeted sequencing
	Tandem mass spectrometry	Enzyme activity assay		Targeted sequencing
Advantages	Inexpensive	Confirmation	Confirmation	Reducing false positives
	Fast		Identification of de novo mutations	Early diagnosis and confirmation
	Suitable for mass screening		Identification of de novo mutations	Identification of de novo mutations
Disadvantages	High false positive rate	Expensive	Expensive	Moderately Expensive
	Low specificity	Semi-quantitative and highly variable	Limited and delayed results	Bioinformatic burden
	Imprecision (10-30%)	Not suitable for potentially oligogenic diseases	Diagnostic odysseys	Need for further valid

Notes

This article is available from http://www.labmedonline.org

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