溶酶体贮积病24种高危筛查及疾病谱分析

High risk screening and disease spectrum for 24 kinds of lysosomal storage diseases

目的评估酶学筛查的敏感性和特异性，探讨华南地区溶酶体贮积病（LSDs）疾病谱特征。方法回顾分析2009年1月至2016年12月在广州市妇女儿童医疗中心就诊的3364例疑似LSDs高危患儿的酶学检测结果，采用人工底物荧光法或比色法检测外周血白细胞或血浆中22种酶活性，筛查24种LSDs疾病，计量资料以面±s表示，计数资料用百分比或构成比表示。结果确诊LSDs患儿283例，共发现18种疾病，高危筛查阳性率为8．4％，其中黏多糖病（MPS）172例（60．8％）、神经鞘脂贮积病79例（27．9％）、Pompe病18例（6．4％）、黏脂病10例（3．5％）、糖蛋白贮积病3例（1．1％）、Wolman病1例（0．4％）。在MPS患儿中，常见类型依次为Ⅱ型（43．6％，75／172例），ⅣA型（26．2％，45／172例）、Vl型（14．0％，24／172例）、I型（11．6％，20／172例）。在神经鞘脂贮积病患儿中，戈谢病和异染性脑白质营养不良（MLD）居多，分别为23例（29．1％）和21例（26．6％）。酶学筛查LSDs的敏感性和特异性均为100％。结论华南地区常见的6种LSDs依次为MPSⅡ型、MPS1VA型、MPSVI、戈谢病、异染性脑白质营养不良及Pompe病。白细胞酶学分析高危筛查LSDs具有高敏感性和特异性。

Objective To evaluate the sensitivity and specificity of enzyme assays, and to provide disease spectrum of lysosomal storage diseases （LSDs）. Methods Three thousand three hundred and sixty - four high risk in-dividuals were screened for 24 LSDs at Guangzhou Women and Children＇s Medical Center between January 2009 and December 2016. Twenty - two kinds of enzyme activities from peripheral blood leucocytes or plasma were measured by using the fluorometry or colorimetry of corresponding artificial snbstrates, screening for 24 LSDs diseases. Measurement data were represented by ~ _＋ s, and count data were expressed as a percentage or composition ratio. Results A total of 283 subjects were diagnosed with 18 different kinds of LSDs, and the positive rate of high - risk screening was 8.4%. Among the identified patients, 172 cases （ 60.8 % ） were mucopolysaccharidosis （ MPS）, 79 cases （ 27.9% ） were sphin-golipidoses,18 cases （6. 4% ） were Pompe diseases, 10 cases （ 3. 5% ） were affected with mucolipidoses, 3 cases （ 1.1% ） were glycoprotein storage diseases,and 1 case（0.4% ） was Wolman disease. Of the MPS cases,there were 75 cases of MPS 1I （43.6%） ,45 cases of MPS ⅣA （26.2%） ,24 cases of MPS VI （ 14.0% ） and 20 cases of MPS I （ 11.6% ）. Gaucher disease （ 23/79 cases, 29. 1% ） and metachromatic leukodystrophy （ MLD ） （ 21/79 cases, 26. 6% ） were common in sphingolipidoses group. Both the sensitivity and specificity of enzyme assays on peripheral blood leucocytes for LSDs were 100%. Conclusions The most common kinds of LSDs are MPS Ⅱ , MPS IV A, MPS VI, Gaucher disease, MLD and Pompe disease. Leukocyte enzymology analysis of high - risk screening LSDs has high sensitivity and specificity.