Diagnosing lysosomal storage diseases in a Brazilian non-newborn population by tandem mass spectrometry
Diagnosing lysosomal storage diseases in a Brazilian non-newborn population by tandem mass spectrometry
复制标题
通过串联质谱诊断巴西非新生儿溶酶体贮积病
作者：
G. Brand;Helainy Cristina de Matos;G. C. N. da Cruz;Nilza do Carmo Fontes;M. Buzzi;J. M. Brum
目的：已经开发出高通量质谱方法来筛查新生儿溶酶体贮积症，从而可以在北美和欧洲实施新生儿筛查试点研究。目前，通过干血斑串联质谱法诊断 Pompe、Fabry、Gaucher、Krabbe 和 Niemann-Pick A/B 病以及粘多糖贮积症 I 是可行的，与标准方法相比，这具有相当大的技术优势。我们的目的是研究最初为新生儿开发的溶酶体贮积病筛查质谱方法是否也可以区分受影响的患者和不同年龄的对照。方法：将 205 名对照个体按年龄分组，采用质谱法定量溶酶体 α-葡萄糖苷酶、β-葡萄糖脑苷脂酶、α-半乳糖苷酶、酸性鞘磷脂酶、半乳脑苷脂酶和 α-L-艾杜糖醛酸酶活性。此外，还对 13 名受影响的患者进行了分析。结果：确定了每种酶和每个年龄组的中位活性。与新生儿相比，18 岁以上个体的酶活性显着降低。受影响患者的酶活性低于年龄匹配对照患者的 20%。结论：我们的数据表明，质谱方法可用于筛查非新生儿患者的溶酶体贮积病。然而，对于某些疾病，例如法布里病和粘多糖贮积症 I，可能需要结合生化和临床数据才能实现准确诊断。
OBJECTIVES: High-throughput mass spectrometry methods have been developed to screen newborns for lysosomal storage disorders, allowing the implementation of newborn screening pilot studies in North America and Europe. It is currently feasible to diagnose Pompe, Fabry, Gaucher, Krabbe, and Niemann-Pick A/B diseases, as well as mucopolysaccharidosis I, by tandem mass spectrometry in dried blood spots, which offers considerable technical advantages compared with standard methodologies. We aimed to investigate whether the mass spectrometry methodology for lysosomal storage disease screening, originally developed for newborns, can also discriminate between affected patients and controls of various ages. METHODS: A total of 205 control individuals were grouped according to age and subjected to mass spectrometry quantification of lysosomal α-glucosidase, β-glucocerebrosidase, α-galactosidase, acid sphingomyelinase, galactocerebrosidase, and α−L-iduronidase activities. Additionally, 13 affected patients were analyzed. RESULTS: The median activities for each enzyme and each age group were determined. Enzyme activities were significantly lower in individuals aged older than 18 years compared with those in newborns. Affected patients presented enzymatic activities corresponding to less than 20% of the age-matched controls. CONCLUSIONS: Our data indicate that the mass spectrometry methodology can be used for the screening of lysosomal storage diseases in non-newborn patients. However, for some diseases, such as Fabry and mucopolysaccharidosis I, a combination of biochemical and clinical data may be necessary to achieve accurate diagnoses.
影响因子：
9.8
作者：
Spada, Marco;Pagliardini, Severo;Desnick, Robert J.
通讯作者：
Desnick, Robert J.