Newborn screening for fabry disease in taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A (IVS4+919G>A)
Journal
Human Mutation
Journal Volume
30
Journal Issue
10
Pages
1397-1405
Date Issued
2009
Author(s)
Chiang S.-C.
Dobrovolny R.
Huang A.-C.
Yeh H.-Y.
Chao M.-C.
Lin S.-J.
Kitagawa T.
Desnick R.J.
Hsu L.-W.
Abstract
Fabry 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
Other Subjects
alpha 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; Taiwan
Type
journal article