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Approaches to diagnostic screening for congenital disorders of glycosylation and its prevalence in Japan

Journal of Human Genetics (2025)Cite this article

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Abstract

Congenital disorders of glycosylation (CDG) represent an emerging and significant category within the spectrum of inborn errors of metabolism. CDG comprise a heterogeneous group of diseases caused by defects at various stages of the glycosylation pathway. Each year, new types of CDG are identified, and to date, pathogenic variants in 189 genes have been associated with over 200 distinct human glycosylation-related disorders. Each type of CDG exhibits characteristic clinical features. Many of CDG result in multisystem involvement, with the central nervous system being particularly affected. Clinical manifestations are highly variable and may include developmental delays, growth impairment, neurological abnormalities such as ataxia, hepatic dysfunction, cardiac defects, coagulation disorders, and abnormal fat distribution. In patients with unexplained neurological symptoms, it is now standard practice to include CDG in the differential diagnosis. Detection of altered glycosylation patterns in serum proteins is essential in the diagnostic evaluation of CDG. Analytical techniques allow the identification of defects in N-glycosylation, O-glycosylation, and combined glycosylation pathways. Once abnormalities in glycosylation are detected, subsequent genetic analysis is necessary to identify causative variants. Our research institute has contributed to the CDG diagnostic support center in Japan by developing novel analytical methods utilizing mass spectrometry. Through these efforts, we have facilitated the molecular diagnosis of 66 patients with CDG across Japan. In this report, we provide an overview of the current landscape of CDG in Japan, along with a summary of the screening and diagnostic processes.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This study was supported by grants from the Japan Agency for Medical Research and Development (Grant nos. 24ek0109614h0003, 21ek0109418h0003).

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Osaka Women’s and Children’s Hospital, Izumi, Japan

    Nobuhiko Okamoto

  2. Department of Molecular Medicine, Research Institute, Osaka Women’s and Children’s Hospital, Izumi, Japan

    Nobuhiko Okamoto, Machiko Kadoya & Yoshinao Wada

  3. Department of Obstetric Medicine, Osaka Women’s and Children’s Hospital, Izumi, Japan

    Yoshinao Wada

Authors
  1. Nobuhiko Okamoto
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  2. Machiko Kadoya
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  3. Yoshinao Wada
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Contributions

All authors contributed to the study conceptualization, design, data collection, analysis, and interpretation of the data, as well as the drafting and revising of the manuscript. NO was responsible for the writing and editing of the final version of the manuscript. YW contributed to the development of glycan analysis techniques. MK performed the practical tasks of mass spectrometry.

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Correspondence to Nobuhiko Okamoto.

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The authors declare no competing interests.

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This study was approved by the institutional review board.

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The procedures in this study were performed in accordance with the ethical standards for medical research outlined in the Helsinki Declaration. Informed consent was obtained from all patients and/or parents included in the study.

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Okamoto, N., Kadoya, M. & Wada, Y. Approaches to diagnostic screening for congenital disorders of glycosylation and its prevalence in Japan. J Hum Genet (2025). https://doi.org/10.1038/s10038-025-01362-w

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