小兒科HWU, WUH-LIANGWUH-LIANGHWUCHIEN, YIN-HSIUYIN-HSIUCHIENLEE, NI- CHUNGNI- CHUNGLEECHIANG, SHU-CHUANSHU-CHUANCHIANGHUANG, AI-CHUAI-CHUHUANGYEH, HUI-YINGHUI-YINGYEHCHAO, MEI-CHYNMEI-CHYNCHAOLIN, SHIO-JEANSHIO-JEANLINHSU, LI-WENLI-WENHSU2010-06-292018-07-112010-06-292018-07-112009http://ntur.lib.ntu.edu.tw//handle/246246/186766Fabry disease (alpha-galactosidase A (alpha-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) alpha-Gal A activities and beta-galactosidase/alpha-Gal A ratios. Of the 90,288 male screenees, 638 (0.7%) had DBS alpha-Gal A activity <30% of normal mean and/or activity ratios >10. A second DBS assay reduced these to 91 (0.1%). Of these, It (including twins) had <5% (Group-A), 64 had 5- 30% (Group-B), and 11 had >30% (Group-C) of mean normal leukocyte alpha- Gal A activity. All 11 GroupA, 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 (similar to 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 phenol type will determine its natural history and optimal timing for therapeutic intervention.en-USFabry diseasealpha-galactosidase A deficiencynewborn screeningGLAjournal article