High Incidence of the Cardiac Variant of Fabry Disease Revealed by Newborn Screening in the Taiwan Chinese Population
High Incidence of the Cardiac Variant of Fabry Disease Revealed by Newborn Screening in the Taiwan Chinese Population
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DOI：
10.1161/circgenetics.109.862920
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发表时间：
2009-10-01
影响因子：
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通讯作者：
Niu, Dau-Ming
中科院分区：
文献类型：
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作者：
Lin, Hsiang-Yu;Chong, Kah-Wai;Niu, Dau-Ming
背景-法布里病是一种可治疗的溶酶体贮积症，这是经常被误诊或迟发diagnosed.Methods和结果，以确定疾病的发病率在中国台湾地区的人口，法布里病新生儿筛查研究开始。通过使用干血点测定α-半乳糖苷酶A（α-Gal A）活性，对110 027例新生儿进行了筛查。在45名新生儿（3名女性）中证实了低血浆α-Gal A活性和法布里突变的存在。鉴定了8种不同的突变，包括3种已知的错义突变（R112 H、A143 T和R356 W），4种新的错义突变（G104 V、M296 L、G360 C和K391 T），和1种已知的内含子突变（IVS 4 + 919 G-> A）。IVS 4 + 919 G-> A突变最常见（82%的患者）。共有20名婴儿的外祖父母携带这种内含子突变进行了评估，超声心动图，突变分析和α-半乳糖苷A活性测定。在9名祖父和11名祖母中发现了内含子突变。在这些祖父母中，3名祖父（33%），但没有祖母患有肥厚性心肌病。另外，对16例诊断为特发性肥厚型心肌病的男性患者进行了突变分析和α-Gal A活性筛查; 4例（25%）显示血浆α-半乳糖苷酶A活性不足并伴有内含子突变。结论-我们发现两个新生儿中心脏变异型法布里病突变IVS 4 + 919 G-> A的发病率出乎意料的高（约1/1600男性）和中国台湾人群中的特发性肥厚型心肌病患者。早期识别未确诊的患者可以及时进行治疗干预，从而提供更好的临床结果。(Circ Genet. 2009;2：450-456）。
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.Conclusion-We found an unexpected high prevalence of the cardiac variant Fabry mutation IVS4 + 919G -> A among both newborns (approximate to 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. (Circ Cardiovasc Genet. 2009;2:450-456.)