{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:23:54Z","timestamp":1783527834005,"version":"3.55.0"},"reference-count":37,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Public Health Genomics"],"abstract":"<jats:p>Introduction: Fabry disease (FD) is a multi-systemic, X-linked lysosomal storage disorder caused by decreased \u03b1-galactosidase activity. Early diagnosis enables timely treatment, but enzyme-based newborn screening (NBS) may not detect affected females. We hypothesized that enzyme-based NBS limitations contribute to sex-based diagnostic disparities in FD and investigated these differences. Methods: Retrospective cohort analyses used data from the Fabry Registry (FR: 2001\u20132023) and Tennessee NBS (2017\u20132024). Sex differences in diagnosis via NBS, biochemical phenotype, symptom onset, and treatment initiation were analyzed using Wilcoxon and chi-square tests. Results: Among 8,657 FR individuals, 73 (67 males, 6 females) were identified via NBS. FR data show that affected females had significantly higher residual \u03b1-galactosidase activity than affected males (leukocyte median: 45.9% vs. 3.9%, plasma median: 32.5% vs. 3.9%; p &lt; 0.0001 for both). FR females had delayed symptom onset (18.1 vs. 11.1 years), later diagnosis (35.5 vs. 30.8 years), and lower treatment rates (51.1% vs. 80.8%) compared to males (all %, p &lt; 0.0001). Tennessee NBS detected 25 males but no females. Conclusion: Females with FD have delays in symptom onset, diagnosis, and treatment compared to males. Furthermore, higher residual enzyme activity causes current enzyme-based NBS to miss most females. Incorporating sex-specific cutoffs and\/or molecular sequencing into NBS could improve early detection and reduce sex-based disparities.<\/jats:p>","DOI":"10.1159\/000552599","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:01:31Z","timestamp":1779379291000},"page":"158-168","source":"Crossref","is-referenced-by-count":0,"title":["Sex-Based Disparities in Fabry Disease Cause Challenges in Newborn Screening"],"prefix":"10.1159","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7278-8242","authenticated-orcid":false,"given":"Yutaka","family":"Furuta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neena S.","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie N.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa 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