The critical role of psychosine in screening, diagnosis, and monitoring of Krabbe disease
The critical role of psychosine in screening, diagnosis, and monitoring of Krabbe disease
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DOI：
10.1038/s41436-020-0764-y
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发表时间：
2020-02-24
影响因子：
8.8
通讯作者：
Matern, Dietrich
中科院分区：
文献类型：
--
作者：
Guenzel, Adam J.;Turgeon, Coleman T.;Matern, Dietrich
目的通过测定半乳糖苷酶（GALC）活性作为克拉伯病（KD）的新生儿筛查（NBS）。这表明GALC活性对KD的特异性较差。Psychosine（PSY）作为一种疾病标志物，可用于降低NBS的假阳性率和疾病监测。我们报告了一个高度敏感的PSY检测，可以识别KD患者与最小的PSY升高。方法以含有d（5）-PSY的甲醇为内标物，从干血斑或红细胞中提取PSY，采用液相色谱-串联质谱法测定。结果对照组（N = 209）、GALC假缺陷携带者（N = 55）、GALC致病性变异携带者（N = 27）、婴儿KD患者（N = 26）和晚发型KD患者（N = 11）的PSY分析允许开发有效的实验室筛查和诊断算法。额外的纵向测量用于追踪造血干细胞移植（HSCT）的治疗效果。结论本研究支持PSY定量作为川崎病NBS的重要组成部分。它有助于区分婴儿型和晚发型KD变体，以及GALC变体和假缺陷携带者。此外，这项研究提供了进一步的数据，PSY测量可以用于监测治疗前后KD的进展。
Purpose Newborn screening (NBS) for Krabbe disease (KD) is performed by measurement of galactocerebrosidase (GALC) activity as the primary test. This revealed that GALC activity has poor specificity for KD. Psychosine (PSY) was proposed as a disease marker useful to reduce the false positive rate for NBS and for disease monitoring. We report a highly sensitive PSY assay that allows identification of KD patients with minimal PSY elevations. Methods PSY was extracted from dried blood spots or erythrocytes with methanol containing d(5)-PSY as internal standard, and measured by liquid chromatography-tandem mass spectrometry. Results Analysis of PSY in samples from controls (N = 209), GALC pseudodeficiency carriers (N = 55), GALC pathogenic variant carriers (N = 27), patients with infantile KD (N = 26), and patients with late-onset KD (N = 11) allowed for the development of an effective laboratory screening and diagnostic algorithm. Additional longitudinal measurements were used to track therapeutic efficacy of hematopoietic stem cell transplantion (HSCT). Conclusion This study supports PSY quantitation as a critical component of NBS for KD. It helps to differentiate infantile from later onset KD variants, as well as from GALC variant and pseudodeficiency carriers. Additionally, this study provides further data that PSY measurement can be useful to monitor KD progression before and after treatment.