Status of newborn screening and follow up investigations for Mucopolysaccharidoses I and II in Taiwan.
Status of newborn screening and follow up investigations for Mucopolysaccharidoses I and II in Taiwan.
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DOI：
10.1186/s13023-018-0816-4
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发表时间：
2018-05-25
影响因子：
3.7
通讯作者：
Lin SP
中科院分区：
文献类型：
--
作者：
Chuang CK;Lin HY;Wang TJ;Huang YH;Chan MJ;Liao HC;Lo YT;Wang LY;Tu RY;Fang YY;Chen TL;Ho HC;Chiang CC;Lin SP
粘多糖贮积症（MPS）是一种溶酶体贮积病，其中编码溶酶体酶的基因突变导致糖胺聚糖（GAG）降解缺陷。GAG在溶酶体中的积累导致细胞功能障碍和临床异常。早期启动酶替代疗法（ERT）可以减缓或预防严重临床表现的发展。MPS I和II新生儿筛查自2015年8月起在台湾推出。召回时复查失败的婴儿被转诊到麦凯纪念医院进行详细的确诊。从2015年8月至2017年11月，分别使用串联质谱对294，196和153，032名婴儿进行了MPS I和MPS II筛查。在这些婴儿中，84例疑似病例（8例为MPS I; 76例为MPS II）被转介确认。首先进行尿一线生化检查，包括尿GAG定量、双向电泳和串联质谱法测定来自GAG的主要二糖。如结果为阳性，则根据白细胞酶测定和分子DNA分析结果进行确诊。从EDTA血液中分离白细胞沉淀，并用于荧光α-艾杜糖醛酸酶（IDUA）或艾杜糖醛酸-2-硫酸酯酶（IDS）酶促测定。还进行了DNA测序分析。在大多数转诊病例中发现了正常的IDS和IDUA酶活性，除了4例强烈怀疑患有MPS I和3例强烈怀疑患有MPS II。在这些婴儿中，有三个IDS基因发生了新的突变，（c.817C > T、c.1025A > G和c.311A > T）和4例IDUA基因有两个错义突变（C.300-3C > G，c.1874A > C; c.1037 T > G，c.1091C > T）分别显示出IDS和IDUA酶活性的显著不足（<平均正常活性的5%）。通过串联质谱法进行的尿硫酸皮肤素和硫酸乙酰肝素定量分析也显示出显著升高。在台湾，MPS I和MPS II的患病率分别为1.35/10万和1.96/10万活产。早期启动ERT治疗MPS可获得更好的临床结局。早期确诊增加了接受适当的医疗护理的可能性，如足够快的ERT，以避免不可逆的表现。到目前为止，本研究中确定的所有高风险婴儿均无症状，并被推定为受减毒疾病变体的影响。
Mucopolysaccharidoses (MPS) are lysosomal storage diseases in which mutations of genes encoding for lysosomal enzymes cause defects in the degradation of glycosaminoglycans (GAGs). The accumulation of GAGs in lysosomes results in cellular dysfunction and clinical abnormalities. The early initiation of enzyme replacement therapy (ERT) can slow or prevent the development of severe clinical manifestations. MPS I and II newborn screening has been available in Taiwan since August 2015. Infants who failed the recheck at recall were referred to MacKay Memorial Hospital for a detailed confirmatory diagnosis. From August 2015 to November 2017, 294,196 and 153,032 infants were screened using tandem mass spectrometry for MPS I and MPS II, respectively. Of these infants, 84 suspected cases (eight for MPS I; 76 for MPS II) were referred for confirmation. Urinary first-line biochemistry examinations were performed first, including urinary GAG quantification, two-dimensional electrophoresis, and tandem mass spectrometry assay for predominant disaccharides derived from GAGs. If the results were positive, a confirmative diagnosis was made according to the results of leukocyte enzymatic assay and molecular DNA analysis. Leukocyte pellets were isolated from EDTA blood and used for fluorescent α-iduronidase (IDUA) or iduronate-2-sulfatase (IDS) enzymatic assay. DNA sequencing analysis was also performed. Normal IDS and IDUA enzyme activities were found in most of the referred cases except for four who were strongly suspected of having MPS I and three who were strongly suspected of having MPS II. Of these infants, three with novel mutations of the IDS gene (c.817C > T, c.1025A > G, and c.311A > T) and four with two missense mutations of the IDUA gene (C.300-3C > G, c.1874A > C; c.1037 T > G, c.1091C > T) showed significant deficiencies in IDS and IDUA enzyme activities (< 5% of mean normal activity), respectively. Urinary dermatan sulfate and heparan sulfate quantitative analyses by tandem mass spectrometry also demonstrated significant elevations. The prevalence rates of MPS I and MPS II in Taiwan were 1.35 and 1.96 per 100,000 live births, respectively. The early initiation of ERT for MPS can result in better clinical outcomes. An early confirmatory diagnosis increases the probability of receiving appropriate medical care such as ERT quickly enough to avoid irreversible manifestations. All high risk infants identified in this study so far remain asymptomatic and are presumed to be affected with the attenuated disease variants.
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影响因子：
2.4
作者：
Jurecka, Agnieszka;Lugowska, Agnieszka;Tylki-Szymanska, Anna
通讯作者：
Tylki-Szymanska, Anna
影响因子：
7.4
作者：
Chennamaneni, Naveen Kumar;Kumar, Arun Babu;Barcenas, Mariana;Spacil, Zdenek;Scott, C. Ronald;Turecek, Frantisek;Gelb, Michael H.
通讯作者：
Gelb, Michael H.
影响因子：
4.2
作者：
Keeratichamroen, S.;Cairns, J. R. Ketudat;Svasti, J.
通讯作者：
Svasti, J.
影响因子：
5.1
作者：
Hopkins, Patrick V.;Campbell, Carlene;Kiesling, Jami
通讯作者：
Kiesling, Jami
影响因子：
5.1
作者：
Burton, Barbara K.;Charrow, Joel;Dizikes, George
通讯作者：
Dizikes, George