title: High incidence of the cardiac variant of Fabry disease revealed by newborn screening in the Taiwan Chinese population.
abstract: BACKGROUND
  Fabry disease is a treatable lysosomal storage disorder, which is often misdiagnosed or belatedly diagnosed.
  
  
  RESULTS
  To determine the disease incidence in the Taiwan Chinese population, a Fabry disease newborn screening study was initiated. A total of 110 027 newborns were screened by assaying the alpha-galactosidase A (alpha-Gal A) activity using dry blood spots. Low plasma alpha-Gal A activity and presence of a Fabry mutation was demonstrated in 45 neonates (3 females). Eight different mutations were identified, including 3 known missense mutations (R112H, A143T, and R356W), 4 novel missense mutations (G104V, M296L, G360C, and K391T), and one known intronic mutation (IVS4+919G-->A). The IVS4+919G-->A mutation was most common (82% of patients). A total of 20 maternal grandparents of infants harboring this intronic mutation were evaluated by echocardiography, mutation analysis and alpha-Gal A activity assay. The intronic mutation was found in 9 grandfathers and 11 grandmothers. Of these grandparents, 3 grandfathers (33%) but none of the grandmothers had hypertrophic cardiomyopathy. Additionally, 16 males who had been diagnosed with idiopathic hypertrophic cardiomyopathy were screened by mutation analysis and alpha-Gal A activity; 4 (25%) showed deficient plasma alpha-Gal A activity in combination with the intronic mutation.
  
  
  CONCLUSIONS
  We found an unexpected high prevalence of the cardiac variant Fabry mutation IVS4+919G-->A among both newborns (approximately 1 in 1600 males) and patients with idiopathic hypertrophic cardiomyopathy in the Taiwan Chinese population. The early identification of undiagnosed patients allows timely therapeutic intervention providing a better clinical outcome.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsiang-Yu
authors.initials: HY
authors.lastname: Lin
authors.forename: Kah-Wai
authors.initials: KW
authors.lastname: Chong
authors.forename: Ju-Hui
authors.initials: JH
authors.lastname: Hsu
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Yu
authors.forename: Chun-Che
authors.initials: CC
authors.lastname: Shih
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Huang
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.forename: Chen-Huan
authors.initials: CH
authors.lastname: Chen
authors.forename: Chuan-Chi
authors.initials: CC
authors.lastname: Chiang
authors.forename: Huey-Jane
authors.initials: HJ
authors.lastname: Ho
authors.forename: Pi-Chang
authors.initials: PC
authors.lastname: Lee
authors.forename: Chuan-Hong
authors.initials: CH
authors.lastname: Kao
authors.forename: Kang-Hsiang
authors.initials: KH
authors.lastname: Cheng
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015997:Neonatal Screening; D010375:Pedigree; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics*
chemical_list: D000519:alpha-Galactosidase