Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria
Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria
复制标题
DOI：
10.1016/s0140-6736(11)61266-x
复制
发表时间：
2012-01-28
期刊：
影响因子：
168.9
通讯作者：
Kasper, David C.
中科院分区：
文献类型：
--
作者：
Mechtler, Thomas P.;Stary, Susanne;Kasper, David C.
背景由于新开发的酶替代疗法、早期诊断的需要和技术的进步，对新生儿筛查溶酶体贮积症的兴趣大大增加。我们在一项匿名的前瞻性全国性筛查研究中检测了戈谢病、庞贝氏病、法布里病和尼曼-皮克病A型和B型，包括基因突变分析，以评估将这些疾病纳入新生儿筛查小组的实用性和适当性。2010年，作为奥地利国家例行新生儿筛查方案的一部分。通过电喷雾电离串联质谱法分析匿名样品的酸性β-葡糖脑苷脂酶、α-半乳糖苷酶、α-葡糖苷酶和酸性鞘磷脂酶的酶活性。基因突变分析疑似酶deficiency.Findings所有34 736个样品进行了成功的多重筛选分析的样本。38例患儿酶活性较低。突变分析证实其中15例为溶酶体贮积症。最常见的突变是法布里病（1/3859出生），其次是庞贝氏病（1/8684）和戈谢氏病（1/17368）。阳性预测值分别为32%（95%CI 16-52）、80%（28-99）和50%（7-93）。突变分析检测主要是错义突变与迟发性phenotype.Interpretation携带突变的溶酶体贮积症的婴儿的总比例高于预期。新生儿筛查溶酶体贮积症可能会给初级卫生保健提供者带来挑战。此外，晚发型突变的高频率使溶酶体贮积症成为儿童期以后的广泛健康问题。
Background The interest in neonatal screening for lysosomal storage disorders has increased substantially because of newly developed enzyme replacement therapies, the need for early diagnosis, and technical advances. We tested for Gaucher's disease, Pompe's disease, Fabry's disease, and Niemann-Pick disease types A and B in an anonymous prospective nationwide screening study that included genetic mutation analysis to assess the practicality and appropriateness of including these disorders in neonatal screening panels.Methods Specimens from dried blood spots of 34 736 newborn babies were collected consecutively from January, 2010 to July, 2010, as part of the national routine Austrian newborn screening programme. Anonymised samples were analysed for enzyme activities of acid beta-glucocerebrosidase, alpha-galactosidase, alpha-glucosidase, and acid sphingomyelinase by electrospray ionisation tandem mass spectrometry. Genetic mutation analyses were done in samples with suspected enzyme deficiency.Findings All 34 736 samples were analysed successfully by the multiplex screening assay. Low enzyme activities were detected in 38 babies. Mutation analysis confirmed lysosomal storage disorders in 15 of them. The most frequent mutations were found for Fabry's disease (1 per 3859 births), followed by Pompe's disease (1 per 8684), and Gaucher's disease (1 per 17 368). The positive predictive values were 32% (95% CI 16-52), 80% (28-99), and 50% (7-93), respectively. Mutational analysis detected predominantly missense mutations associated with a late-onset phenotype.Interpretation The combined overall proportion of infants carrying a mutation for lysosomal storage disorders was higher than expected. Neonatal screening for lysosomal storage disorders is likely to raise challenges for primary health-care providers. Furthermore, the high frequency of late-onset mutations makes lysosomal storage disorders a broad health problem beyond childhood.