Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy

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 p...

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Main Authors: Takanori Onuki, Makiko Tajika, Yohei Sugiyama, Masaru Shimura, Keiko Ichimoto, Toju Tanaka, Hiromi Nyuzuki, Motomichi Kosuga, Ohsuke Migita, Tetsuya Ito, Hideo Sasai, Ryosuke Bo, Junpei Hamada, Takashi Hamazaki, Norio Sakai, Takahito Inoue, Kimitoshi Nakamura, Torayuki Okuyama, Kei Murayama
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Orphanet Journal of Rare Diseases
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Online Access:https://doi.org/10.1186/s13023-025-03848-4
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author Takanori Onuki
Makiko Tajika
Yohei Sugiyama
Masaru Shimura
Keiko Ichimoto
Toju Tanaka
Hiromi Nyuzuki
Motomichi Kosuga
Ohsuke Migita
Tetsuya Ito
Hideo Sasai
Ryosuke Bo
Junpei Hamada
Takashi Hamazaki
Norio Sakai
Takahito Inoue
Kimitoshi Nakamura
Torayuki Okuyama
Kei Murayama
author_facet Takanori Onuki
Makiko Tajika
Yohei Sugiyama
Masaru Shimura
Keiko Ichimoto
Toju Tanaka
Hiromi Nyuzuki
Motomichi Kosuga
Ohsuke Migita
Tetsuya Ito
Hideo Sasai
Ryosuke Bo
Junpei Hamada
Takashi Hamazaki
Norio Sakai
Takahito Inoue
Kimitoshi Nakamura
Torayuki Okuyama
Kei Murayama
author_sort Takanori Onuki
collection DOAJ
description 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.
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publishDate 2025-07-01
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spelling doaj-art-2dcb9c1cc5c54f74a046e5a397fc172a2025-08-20T03:42:07ZengBMCOrphanet Journal of Rare Diseases1750-11722025-07-012011910.1186/s13023-025-03848-4Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophyTakanori Onuki0Makiko Tajika1Yohei Sugiyama2Masaru Shimura3Keiko Ichimoto4Toju Tanaka5Hiromi Nyuzuki6Motomichi Kosuga7Ohsuke Migita8Tetsuya Ito9Hideo Sasai10Ryosuke Bo11Junpei Hamada12Takashi Hamazaki13Norio Sakai14Takahito Inoue15Kimitoshi Nakamura16Torayuki Okuyama17Kei Murayama18Department of Metabolism, Center for Medical Genetics, Chiba Children’s HospitalDepartment of Metabolism, Center for Medical Genetics, Chiba Children’s HospitalDepartment of Metabolism, Center for Medical Genetics, Chiba Children’s HospitalDepartment of Metabolism, Center for Medical Genetics, Chiba Children’s HospitalDepartment of Metabolism, Center for Medical Genetics, Chiba Children’s HospitalDepartment of Pediatrics, National Hospital Organization Hokkaido Medical CenterDivision of Pediatrics, Department of Homeostatic Regulation and Development, Graduate School of Medical and Dental Sciences, Niigata UniversityDivision of Medical Genetics, National Center for Child Health and Development, Department of Pediatrics, St. Marianna University School of MedicineDepartment of Pediatrics, School of Medicine, Fujita Health UniversityDepartment of Pediatrics, Gifu University Graduate School of MedicineDepartment of Pediatrics, Kobe University Graduate School of MedicineDepartment of Pediatrics, Graduate School of Medicine, Ehime UniversityDepartment of Pediatrics, Graduate School of Medicine, Osaka Metropolitan UniversityCenter for Promoting Treatment of Intractable Diseases, ISEIKAI International General HospitalDepartment of Pediatrics, Fukuoka University Chikushi HospitalDepartment of Pediatrics, Faculty of Life Sciences, Kumamoto UniversityDepartment of Clinical Genomics, Saitama Medical UniversityDepartment of Metabolism, Center for Medical Genetics, Chiba Children’s HospitalAbstract 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.https://doi.org/10.1186/s13023-025-03848-4Newborn screeningNBSLysosomal storage diseaseLSDAdrenoleukodystrophyALD
spellingShingle Takanori Onuki
Makiko Tajika
Yohei Sugiyama
Masaru Shimura
Keiko Ichimoto
Toju Tanaka
Hiromi Nyuzuki
Motomichi Kosuga
Ohsuke Migita
Tetsuya Ito
Hideo Sasai
Ryosuke Bo
Junpei Hamada
Takashi Hamazaki
Norio Sakai
Takahito Inoue
Kimitoshi Nakamura
Torayuki Okuyama
Kei Murayama
Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy
Orphanet Journal of Rare Diseases
Newborn screening
NBS
Lysosomal storage disease
LSD
Adrenoleukodystrophy
ALD
title Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy
title_full Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy
title_fullStr Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy
title_full_unstemmed Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy
title_short Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy
title_sort japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy
topic Newborn screening
NBS
Lysosomal storage disease
LSD
Adrenoleukodystrophy
ALD
url https://doi.org/10.1186/s13023-025-03848-4
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