High incidence of the cardiac variant of fabry disease revealed by newborn screening in the Taiwan Chinese population

Hsiang Yu Lin, Kah Wai Chong, Ju Hui Hsu, Hsiao Chi Yu, Chun Che Shih, Cheng Hung Huang, Shing Jong Lin, Chen Huan Chen, Chuan Chi Chiang, Huey Jane Ho, Pi Chang Lee, Chuan Hong Kao, Kang Hsiang Cheng, Chuen Hsueh, Dau Ming Niu

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Background-Fabry disease is a treatable lysosomal storage disorder, which is often misdiagnosed or belatedly diagnosed. Methods and 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 α-galactosidase A (α-Gal A) activity using dry blood spots. Low plasma α-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+919G3→A). The IVS4+919G3→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 α-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 α-Gal A activity; 4 (25%) showed deficient plasma α-Gal A activity in combination with the intronic mutation. Conclusion-We found an unexpected high prevalence of the cardiac variant Fabry mutation IVS4+919G3→A among both newborns (=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.

Original languageEnglish
Pages (from-to)450-456
Number of pages7
JournalCirculation: Cardiovascular Genetics
Volume2
Issue number5
DOIs
Publication statusPublished - Oct 1 2009
Externally publishedYes

Fingerprint

Taiwan
Newborn Infant
Mutation
Incidence
Population
Hypertrophic Cardiomyopathy
Fabry Disease
Missense Mutation
Cardiac Variant Fabry Disease
Galactosidases
Diagnostic Errors
Echocardiography
Grandparents
Mothers

Keywords

  • Fabry disease
  • Hypertrophic cardiomyopathy
  • Hypertrophy
  • Newborn screening
  • Taiwan Chinese population

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

High incidence of the cardiac variant of fabry disease revealed by newborn screening in the Taiwan Chinese population. / Lin, Hsiang Yu; Chong, Kah Wai; Hsu, Ju Hui; Yu, Hsiao Chi; Shih, Chun Che; Huang, Cheng Hung; Lin, Shing Jong; Chen, Chen Huan; Chiang, Chuan Chi; Ho, Huey Jane; Lee, Pi Chang; Kao, Chuan Hong; Cheng, Kang Hsiang; Hsueh, Chuen; Niu, Dau Ming.

In: Circulation: Cardiovascular Genetics, Vol. 2, No. 5, 01.10.2009, p. 450-456.

Research output: Contribution to journalArticle

Lin, HY, Chong, KW, Hsu, JH, Yu, HC, Shih, CC, Huang, CH, Lin, SJ, Chen, CH, Chiang, CC, Ho, HJ, Lee, PC, Kao, CH, Cheng, KH, Hsueh, C & Niu, DM 2009, 'High incidence of the cardiac variant of fabry disease revealed by newborn screening in the Taiwan Chinese population', Circulation: Cardiovascular Genetics, vol. 2, no. 5, pp. 450-456. https://doi.org/10.1161/CIRCGENETICS.109.862920
Lin, Hsiang Yu ; Chong, Kah Wai ; Hsu, Ju Hui ; Yu, Hsiao Chi ; Shih, Chun Che ; Huang, Cheng Hung ; Lin, Shing Jong ; Chen, Chen Huan ; Chiang, Chuan Chi ; Ho, Huey Jane ; Lee, Pi Chang ; Kao, Chuan Hong ; Cheng, Kang Hsiang ; Hsueh, Chuen ; Niu, Dau Ming. / High incidence of the cardiac variant of fabry disease revealed by newborn screening in the Taiwan Chinese population. In: Circulation: Cardiovascular Genetics. 2009 ; Vol. 2, No. 5. pp. 450-456.
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abstract = "Background-Fabry disease is a treatable lysosomal storage disorder, which is often misdiagnosed or belatedly diagnosed. Methods and 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 α-galactosidase A (α-Gal A) activity using dry blood spots. Low plasma α-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+919G3→A). The IVS4+919G3→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 α-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 α-Gal A activity; 4 (25{\%}) showed deficient plasma α-Gal A activity in combination with the intronic mutation. Conclusion-We found an unexpected high prevalence of the cardiac variant Fabry mutation IVS4+919G3→A among both newborns (=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.",
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AU - Ho, Huey Jane

AU - Lee, Pi Chang

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KW - Hypertrophic cardiomyopathy

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