Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 24;20(1):373.
doi: 10.1186/s13023-025-03848-4.

Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy

Takanori Onuki #  1   2 , Makiko Tajika #  1 , Yohei Sugiyama  1 , Masaru Shimura  1 , Keiko Ichimoto  1 , Toju Tanaka  3 , Hiromi Nyuzuki  2 , Motomichi Kosuga  4 , Ohsuke Migita  5 , Tetsuya Ito  6 , Hideo Sasai  7 , Ryosuke Bo  8 , Junpei Hamada  9 , Takashi Hamazaki  10 , Norio Sakai  11 , Takahito Inoue  12 , Kimitoshi Nakamura  13 , Torayuki Okuyama  14 , Kei Murayama  15   16   17
Affiliations

Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy

Takanori Onuki et al. Orphanet J Rare Dis. .

Abstract

Background: Recently, Newborn screening (NBS) has been expanded worldwide to include lysosomal storage diseases (LSDs) and adrenoleukodystrophy (ALD) due to the importance of early diagnosis and early treatment. In Japan, NBS for LSDs, termed expanded NBS, was first implemented in Kumamoto prefecture in 2006 as pilot study. NBS for ALD was subsequently introduced in Aichi prefecture and Gifu prefecture in 2021. Expanded NBS for LSDs and ALD has become more widespread in Japan. In light of this current situation, we considered it is necessary to clarify the usefulness of expanded NBS, prevalence of each disease, challenges encountered. Therefore, we reported the current implementation status of expanded NBS in Japan.

Method: A survey was conducted among physicians responsible for expanded NBS in each target region Japan. The target regions were those that implemented NBS for LSDs and/or ALD for more than one year. The survey items included: the entity conducting expanded NBS, the facilities conducting the tests, the target areas, medical institutions for close examination such as detailed biochemical analysis and/or genetic sequencing, and treatments, types of target diseases, fee for NBS, sample collection methods, testing method, and quantitative data on expanded NBS, retesting, and diagnoses in each area.

Results: Responses were received from nine regions and an organization (CReARID). The total number of 733,838 newborns were screening, with 101 diagnoses: 75 cases of Fabry disease, 10 of mucopolysaccharidosis (MPS) II, 8 of Pompe disease, 5 of Gaucher disease, 2 of MPS I, 1 of ALD, respectively) were diagnosed. More cases were diagnosed with the target disease than the estimated prevalence. In contrast, the positive predictive value was low and false-positive rates was elevated, particularly for PD, MPS II, and ALD, have been attributed to pseudodeficiency alleles and methodological differences. Moreover, variant of unknown significance (VUS) in the ABCD1 gene was detected in many of the patients with suspected ALD.

Conclusion: In Japan, Expanded NBS for LSDs and ALD has become more widespread. Since its implementation, some patients have been diagnosed and received treatment. However, challenges such as pseudodeficiency, indications, testing methods, and VUS that require improvement.

Keywords: ALD; Adrenoleukodystrophy; LSD; Lysosomal storage disease; NBS; Newborn screening.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Informed Consent: Ethical principles of this study were conducted in accordance with the guidelines of the Declaration of Helsinki. Consent for publication: Not applicable.

Figures

Fig. 1
Fig. 1
Expanded NBS Area Map in Japan. A map showing areas where expanded NBS for LSDs/ALD is implemented in Japan. Black areas represented areas where NBS is implemented throughout the regions: Hokkaido prefecture, Niigata prefecture, Gunma prefecture, Gifu prefecture, Aichi prefecture, Hyogo prefecture, Ehime prefecture, Fukuoka prefecture, Okinawa prefecture. The grey areas are areas that are implemented in some regions; Ibaraki prefecture, Saitama prefecture, Chiba prefecture, Tokyo Metropolis, Kanagawa prefecture, Shizuoka prefecture, Shiga prefecture, Osaka prefecture, and Wakayama prefecture
See this image and copyright information in PMC

References

    1. Martina JA, Raben N, Puertollano R. SnapShot: lysosomal storage diseases. Cell. 2020;180(3):602-602.e1. 10.1016/j.cell.2020.01.017. - DOI - PMC - PubMed
    1. Gupta AO, Raymond G, Pierpont EI, Kemp S, McIvor RS, Rayannavar A, Miller B, Lund TC, Orchard PJ. Treatment of cerebral adrenoleukodystrophy: allogeneic transplantation and lentiviral gene therapy. Expert Opin Biol Ther. 2022;22(9):1151–62. 10.1080/14712598.2022.2124857. - DOI - PubMed
    1. Biffi A, Montini E, Lorioli L, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013;341(6148):1233158. 10.1126/science.1233158. - DOI - PubMed
    1. Videbæk C, Melgaard L, Lund AM, Grønborg SW. Newborn screening for adrenoleukodystrophy: International experiences and challenges. Mol Genet Metab. 2023;140(4): 107734. 10.1016/j.ymgme.2023.107734. - DOI - PubMed
    1. Zhu J, Eichler F, Biffi A, Duncan CN, Williams DA, Majzoub JA. The changing face of adrenoleukodystrophy. Endocr Rev. 2020;41(4):577–93. 10.1210/endrev/bnaa013. - DOI - PMC - PubMed

Supplementary concepts