Newborn screening for Fabry disease in Japan: an additional 3-year report

Newborn screening (NBS) for Fabry disease (FD) is highly effective at detecting FD prior to symptom onset. This initiative is currently being implemented worldwide. We previously reported results for 599,711 newborns from the first large-scale NBS program for FD in Japan, from August 2006 to December 2018. In this study, we provide additional data from January 2019 to September 2022. A total of 782,591 newborns were screened, and 29 variants, including 18 pathogenic variants and 11 variants of uncertain significance (VUS), were detected in 77 newborns (57 males and 20 females). Thirty-five male and 14 female newborns with pathogenic variants in GLA were identified. Twenty-two male and six female newborns with VUS in GLA were also identified. At the most recent follow-up, 5 of the 35 hemizygous patients manifested symptoms or signs and were receiving enzyme replacement therapy. The estimated frequency of patients with FD, including individuals with pathogenic variants or VUS identified in this study, was 1 in 7730, whereas that of patients with pathogenic variants was 1:12,436. FD-related cardiac and renal tissue damage are present before the onset of FD symptoms, such as limb pain. These findings highlight the importance of early diagnosis using NBS and regular monitoring.