WUH-LIANG HWUYIN-HSIU CHIENNI-CHUNG LEEChiang S.-C.Dobrovolny R.Huang A.-C.Yeh H.-Y.Chao M.-C.Lin S.-J.Kitagawa T.Desnick R.J.Hsu L.-W.2020-12-092020-12-0920091059-7794https://www.scopus.com/inward/record.uri?eid=2-s2.0-73349136303&doi=10.1002%2fhumu.21074&partnerID=40&md5=e8333c802e005e45da4c87467666847bhttps://scholars.lib.ntu.edu.tw/handle/123456789/525175Fabry disease (α-galactosidase A (α-Gal A, GLA) deficiency) is a panethnic inborn error of glycosphingolipid metabolism. Because optimal therapeutic outcomes depend on early intervention, a pilot program was designed to assess newborn screening for this disease in 171,977 consecutive Taiwanese newborns by measuring their dry blood spot (DBS) α-Gal A activities and β-galactosidase/α-Gal A ratios. Of the 90,288 male screenees, 638 (0.7%) had DBS α-Gal A activity <30% of normal mean and/or activity ratios >10. A second DBS assay reduced these to 91 (0.1%). Of these, 11 (including twins) had <5% (Group-A), 64 had 5-30% (Group-B), and 11 had >30% (Group-C) of mean normal leukocyte α-Gal A activity. All 11 Group-A, 61 Group-B, and 1 Group-C males had GLA gene mutations. Surprisingly, 86% had the later-onset cryptic splice mutation c.936+919G>A (also called IVS4+ 919G>A). In contrast, screening 81,689 females detected two heterozygotes. The novel mutations were expressed in vitro, predicting their classical or later-onset phenotypes. Newborn screening identified a surprisingly high frequency of Taiwanese males with Fabry disease (~1 in 1,250), 86% having the IVS4+919G>A mutation previously found in later-onset cardiac phenotype patients. Further studies of the IVS4 later-onset phenotype will determine its natural history and optimal timing for therapeutic intervention. ? 2009 Wiley-Liss, Inc.[SDGs]SDG3alpha galactosidase; amino acid sequence; article; chemistry; Fabry disease; female; genetics; human; incidence; male; molecular genetics; newborn; newborn screening; onset age; pedigree; phenotype; sequence homology; Taiwan; Age of Onset; alpha-Galactosidase; Amino Acid Sequence; Fabry Disease; Female; Humans; Incidence; Infant, Newborn; Male; Molecular Sequence Data; Neonatal Screening; Pedigree; Phenotype; Sequence Homology, Amino Acid; Taiwanjournal article10.1002/humu.21074196214172-s2.0-73349136303