Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A (IVS4+919G>A)

Hum Mutat. 2009 Oct;30(10):1397-405. doi: 10.1002/humu.21074.


Fabry 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, 11 (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 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 (approximately 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Amino Acid Sequence
  • Fabry Disease / diagnosis*
  • Fabry Disease / epidemiology
  • Fabry Disease / genetics
  • Female
  • Humans
  • Incidence
  • Infant, Newborn
  • Male
  • Molecular Sequence Data
  • Neonatal Screening*
  • Pedigree
  • Phenotype
  • Sequence Homology, Amino Acid
  • Taiwan / epidemiology
  • alpha-Galactosidase / chemistry
  • alpha-Galactosidase / genetics*


  • alpha-Galactosidase