A selective screening program for the early detection of mucopolysaccharidosis: Results of the FIND project - a 2-year follow-up study.
A selective screening program for the early detection of mucopolysaccharidosis: Results of the FIND project - a 2-year follow-up study.
复制标题
DOI：
10.1097/md.0000000000006887
复制
发表时间：
2017-05
期刊：
影响因子：
1.6
通讯作者：
Couce ML
中科院分区：
文献类型：
--
作者：
Colón C;Alvarez JV;Castaño C;Gutierrez-Solana LG;Marquez AM;O'Callaghan M;Sánchez-Valverde F;Yeste C;Couce ML
粘多糖病(MPSS)被低估了，但很少有新生儿筛查项目对其进行评估，这可能是因为仍然存在许多挑战，如晚发性表型的鉴定。在临床症状开始时进行系统筛查可以帮助及早确定哪些患者可能从特定的治疗中受益。这项前瞻性研究的目的是评估一项新的选择性筛查计划，即FIND项目，目标是0至16岁有MPS临床表现的患者。该项目旨在提高儿科医生对这些疾病的认识，并使其能够早期诊断。从2014年7月到2016年6月，在儿科医生提交的尿液分析论文中测定了归一化为肌酐水平的糖胺多糖(GAG)水平，这些分析论文的患者的临床体征和/或症状与MPS相符。当检测到高浓度的GAG时，需要新的液体尿样来确认和鉴定GAG的存在。当怀疑是特定形式的MPS时，用血液浸渍纸法分析酶活性，以确定MPS的类型(I、IIIB、IIIC、IVA、IVB、VI或VII)。GAG的年龄特定参考值之前是使用145个健康儿童的尿样建立的。在收到的180份初始样本中，147份(81.7%)的GAG水平正常。另外33例(18.3%)需要液体样本；其中13例GAG水平正常，12例轻微升高，尽管电泳法研究没有显示MPS的证据。8例证实为酶活性升高和相应的酶活性降低。从出现临床症状到检测到MPS的平均时间为22个月，仅在项目开始时发现2例，临床症状演变分别为35个月和71个月。我们的MPS筛查策略的敏感性为100%，特异性为85%，阳性预测值为24%。FIND项目是一种有用且具有成本效益的筛查方法，可提高儿科医生对MPS的认识，并能够在临床症状出现时检测MPS。
The mucopolysaccharidoses (MPSs) are underdiagnosed but they are evaluated in few newborn screening programs, probably due to the many challenges remaining, such as the identification of late-onset phenotypes. Systematic screening at the onset of clinical symptoms could help to early identify patients who may benefit from specific treatments. The aim of this prospective study was to assess a novel selective screening program, the FIND project, targeting patients aged 0 to 16 years with clinical manifestations of MPS. The project was designed to increase awareness of these diseases among pediatricians and allow early diagnosis. From July 2014 to June 2016, glycosaminoglycan (GAG) levels normalized to creatinine levels were determined in urine-impregnated analytical paper submitted by pediatricians who had patients with clinical signs and/or symptoms compatible with MPS. When high GAG concentrations were detected, a new liquid urine sample was requested to confirm and identify the GAG present. When a specific form of MPS was suspected, enzyme activity was analyzed using blood-impregnated paper to determine MPS type (I, IIIB, IIIC, IVA, IVB, VI, or VII). Age-specific reference values for GAG were previously established using 145 urine samples from healthy children. GAG levels were normal in 147 (81.7%) of the 180 initial samples received. A liquid sample was requested for the other 33 cases (18.3%); GAG levels were normal in 13 of these and slightly elevated in 12, although the electrophoresis study showed no evidence of MPS. Elevated levels with corresponding low enzymatic activity were confirmed in 8 cases. The mean time from onset of clinical symptoms to detection of MPS was 22 months, and just 2 cases were detected at the beginning of the project were detected with 35 and 71 months of evolution of clinical symptoms. Our screening strategy for MPS had a sensitivity of 100%, a specificity of 85%, and a positive predictive value of 24%. The FIND project is a useful and cost-effective screening method for increasing awareness of MPS among pediatricians and enabling the detection of MPS at onset of clinical symptoms.