Disease-specific markers for the mucopolysaccharidoses
Disease-specific markers for the mucopolysaccharidoses
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DOI：
10.1203/01.pdr.0000141987.69757.dd
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发表时间：
2004-11-01
影响因子：
3.6
通讯作者：
Meikle, PJ
中科院分区：
文献类型：
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作者：
Fuller, M;Rozaklis, T;Meikle, PJ
随着我们进入一个推进粘多糖剂量（MPS）治疗机会的时代，对临床医生的早期诊断提出了前所未有的要求。任何治疗途径的生化监测也将是先决条件。为此，我们旨在确定一系列可用于识别和表征MPS患者的尿寡糖。我们分析了94个尿液样本，从68例MPS和26个控制个人的寡糖来自糖胺聚糖使用电喷雾电离串联质谱。将每个患者组的寡糖谱与对照组进行比较。使用Mann-Whitney U检验测量每个患者组与对照组之间的每种分析物差异。还对骨髓移植前和移植后连续时间的患者尿样进行了评价。在每种NIPS亚型的尿液中鉴定了许多寡糖，并针对每种寡糖，制定了特定的寡糖谱。这些特征能够识别所有68例患者及其亚型，MPS IIIB和IIIC除外。选定的低聚糖被用来评估三个人骨髓移植后，并在每种情况下，大量减少诊断性低聚糖，移植后，观察。尿中糖胺聚糖衍生的寡糖的鉴定和测量为MPS个体的早期鉴定提供了灵敏和特异的筛选。由此产生的寡糖谱不仅表征亚型，而且还为当前和拟议的治疗的生化监测提供疾病特异性指纹。
Unprecedented demands are now placed on clinicians for early diagnosis as we enter into an era of advancing treatment opportunities for the mucopolysacchari doses (MPS). Biochemical monitoring of any therapeutic avenue will also be prerequisite. To this end, we aimed to identify a range of urinary oligosaccharides that could be used to identify and characterize patients with MPS. We analyzed 94 urine samples from 68 patients with MPS and 26 control individuals for oligosaccharides derived from glycosaminoglycans using electrospray ionization-tandem mass spectrometry. The oligosaccharide profile for each patient group was compared with that of the control group. The Mann-Whitney U test was used to measure the difference between each patient group and the controls for each analyte. Urine samples from patients before and at successive times after bone marrow transplantation were also evaluated. A number of oligosaccharides were identified in the urine of each NIPS subtype, and for each of these, specific oligosaccharide profiles were formulated. These profiles enabled the identification of all 68 patients and their subtypes with the exception of MPS IIIB and IIIC. Selected oligosaccharides were used to assess three individuals after a bone marrow transplant, and, in each case, a substantial reduction in the level of diagnostic oligosaccharides, posttransplantation, was observed. The identification and measurement of glycosaminoglycan-derived oligosaccharides in urine provides a sensitive and specific screen for the early identification of individuals with MPS. The resulting oligosaccharide profiles not only characterize subtype but also provide a disease-specific fingerprint for the biochemical monitoring of current and proposed therapies.