Sensitivity and specificity of decreased CSF asialotransferrin for eIF2B-related disorder
Sensitivity and specificity of decreased CSF asialotransferrin for eIF2B-related disorder
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DOI：
10.1212/01.wnl.0000313857.54398.0e
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发表时间：
2008-06-03
期刊：
影响因子：
9.9
通讯作者：
Schiffmann, R.
中科院分区：
文献类型：
--
作者：
Vanderver, A.;Hathout, Y.;Schiffmann, R.
目的：以临床评价和eIF2B突变分析为参考标准，评价CSF asialotransferrin / transferrin比值测定对eIF2B相关疾病的诊断准确性。EIF2B相关疾病是一种相对常见的白质营养不良，具有广泛的表型变异，可由五种EIF2B基因中的任何一种突变引起。有一个简单的和临床有效的筛选工具，为医生评估患者与未分类脑白质营养不良的需要。方法：对6例EIF2B基因突变患者、其他类型脑白质营养不良患者和无脑白质营养不良患者进行脑脊液二维凝胶（2DG）电泳测定asialotransferrin / transferrin比率。结果：与54名未受CSF 2DG分析影响的对照组相比，所有6名突变证实eif2b相关疾病的患者脑脊液中asialotransferrin的含量低至几乎检测不到。eif2b样患者临床表现相似，但没有EIF2B1-5突变，通过该生物标志物将其与EIF2B1-5突变患者区分开来。EIF2B1-5突变患者的asialotransferrin/transferrin比值水平与整体组有显著差异（p < 0.001）。以8%的asialotransferrin/transferrin比值作为临界值，该生物标志物具有100%的敏感性（95% CI = 52-100%）和94%的特异性（95% CI = 84-99%）。结论：eif2 - b相关疾病患者脑脊液asialotransferrin/ transferrin比值降低具有高度敏感性和特异性。这种快速（< 48小时）和廉价的eif2b相关疾病诊断工具有潜力识别可能与eif2b相关疾病的患者进行突变分析。
Objective: This is a study estimating diagnostic accuracy of CSF asialotransferrin to transferrin ratio measurement in eIF2B related disorders by using clinical evaluation and EIF2B mutation analysis as the reference standard. eIF2B-related disorder is a relatively common leukodystrophy with broad phenotypic variation that is caused by mutations in any of the five EIF2B genes. There is a need for a simple and clinically valid screening tool for physicians evaluating patients with an unclassified leukodystrophy.Methods: CSF two-dimensional gel (2DG) electrophoresis analyses to measure asialotransferrin to transferrin ratios were performed in 60 subjects including 6 patients with documented EIF2B gene mutations, patients with other types of leukodystrophy, and patients with no leukodystrophy.Results: All six patients with mutation proven eIF2B-related disease showed low to nearly undetectable amounts of asialotransferrin in their CSF when compared to 54 unaffected controls by CSF 2DG analyses in this study. eIF2B-like patients, with clinically similar presentations but no mutations in EIF2B1-5, were distinguished from patients with mutations in EIF2B1-5 by this biomarker. Patients with mutations in EIF2B1-5 had asialotransferrin/transferrin ratio levels significantly different from the group as a whole (p < 0.001). Using 8% asialotransferrin/transferrin ratio as a cutoff, this biomarker has a 100% sensitivity (95% CI = 52-100%) and 94% specificity (95% CI = 84-99%).Conclusion: Decreased asialotransferrin/ transferrin ratio in the CSF of patients with eIF2-Brelated disorder is highly sensitive and specific. This rapid (< 48 hours) and inexpensive diagnostic tool for eIF2B-related disorders has the potential to identify patients with likely eIF2B-related disorder for mutation analysis.