Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy

Abstract Background: Recently, Newborn screening (NBS) has been extended worldwide to include Lysosomal storage diseases (LSDs) and adrenoleukodystrophy (ALD) as the importance of early diagnosis and early treatment. In Japan, NBS for LSDs, called expanded NBS, started in Kumamoto prefecture in 2006 as pilot study. NBS For ALD started in Aichi prefecture and Gifu prefecture in 2021. Expanded NBS for LSDs and ALD has spread increasingly in Japan. In light of this current situation, we considered it is necessary to clarify the usefulness of expanded NBS, prevalence of each disease, problems and issues. Therefore, we reported the current status of expanded NBS in Japan. Method: A survey was conducted on representative physicians of expanded NBS in each target region Japan. The target regions were regions conducting NBS for LSDs and/or ALD for more than one year. The survey items were as follows: 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 the number of taking 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 tested, of whom 101 (75 with FD, 10 with mucopolysaccharidosis [MPS] II, 8 with Pompe disease [PD], 5 with Gaucher disease [GD], 2 with MPS I, 1 with 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 high, 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 is spreading increasingly. Some patients were diagnosed and received treatment. However, there are problems such as pseudodeficiency, indications, testing methods, and VUS that require improvement.