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.
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.
Authors: W Terryn; R Vanholder; D Hemelsoet; B P Leroy; W Van Biesen; G De Schoenmakere; B Wuyts; K Claes; J De Backer; G De Paepe; A Fogo; M Praet; B Poppe Journal: JIMD Rep Date: 2012-07-29
Authors: Linda Sigmundsdottir; Michel C Tchan; Alex A Knopman; Graham C Menzies; Jennifer Batchelor; David O Sillence Journal: Arch Clin Neuropsychol Date: 2014-11 Impact factor: 2.813