A new integrated newborn screening workflow can provide a shortcut to differential diagnosis and confirmation of inherited metabolic diseases

Jung Min Ko, Kyung Sun Park, Yeeok Kang, Seong Hyeuk Nam, Yoonjung Kim, Inho Park, Hyun Wook Chae, Soon Min Lee, Kyung A. Lee, Jong Won Kim

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Purpose: We developed a new workflow design which included results from both biochemical and targeted gene sequencing analysis interpreted comprehensively. We then conducted a pilot study to evaluate the benefit of this new approach in newborn screening (NBS) and demonstrated the efficiency of this workflow in detecting causative genetic variants. Materials and Methods: Ten patients in Group 1 were diagnosed clinically using biochemical assays only, and 10 newborns in Group 2 were diagnosed with suspected inherited metabolic disease (IMD) in NBS. We applied NewbornDiscovery (SD Genomics), an integrated workflow design that encompasses analyte-phenotype-gene, single nucleotide variant/small insertion and dele-tion/copy number variation analyses along with clinical interpretation of genetic variants related to each participant’s condition. Results: A molecular genetic diagnosis was established in 95% (19/20) of individuals. In Group 1, 13 and 7 of 20 alleles were classified as pathogenic and likely pathogenic, respectively. In Group 2, 11 and 6 of 17 alleles with identified causative variants were pathogenic and likely pathogenic, respectively. There were no variants of uncertain significance. For each individual, the NewbornDiscovery and biochemical analysis results reached 100% concordance, since the single newborn testing negative for causative genetic variant in Group 2 showed a benign clinical course. Conclusion: This integrated diagnostic workflow resulted in a high yield. This approach not only enabled early confirmation of specific IMD, but also detected conditions not included in the current NBS.

Original languageEnglish
Pages (from-to)652-661
Number of pages10
JournalYonsei medical journal
Issue number5
Publication statusPublished - 2018 Jul

Bibliographical note

Funding Information:
The study was supported by grant A120030 from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea.

Publisher Copyright:
© Yonsei University College of Medicine 2018.

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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