High incidence of the cardiac variant of Fabry disease revealed by newborn screening in the Taiwan Chinese population - PubMed (original) (raw)

doi: 10.1161/CIRCGENETICS.109.862920. Epub 2009 Jul 24.

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

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

Hsiang-Yu Lin et al. Circ Cardiovasc Genet. 2009 Oct.

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 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.

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