Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
Sci Rep. 2024 Oct 3;14(1):23033. doi: 10.1038/s41598-024-73537-y.
Fabry disease (FD) constitutes a rare, X-linked lysosomal storage disorder affecting multiple organ systems, most notably heart, kidneys, and the central nervous system. Neurofilament light chains (NfL) have emerged as a prime candidate for a body fluid biomarker reflecting neuro-axonal injury. We aimed to evaluate its addition to the diagnostic and monitoring armamentarium in FD. Serum NfL concentrations (sNfL) were measured in 50 people with FD (PwFD) and 30 healthy control subjects (HC) using the Simoa© technology, followed by calculation of Z-scores adjusted for age and body mass index. In addition, clinical disease severity in PwFD was measured using the FOS-MSSI (Fabry outcome study - Mainz severity score index), which comprises clinical and paraclinical parameters. PwFD show elevated sNfL Z-scores compared to HC (PwFD: 1.12 [SD 1.5], HC: 0.01 [SD 1.2], p < 0.001). In PwFD, males showed higher sNfL Z-scores than females (1.75 [SD 1.5] vs. 0.73 [SD 1.4]). Importantly, sNfL Z-scores were increased in PwFD with ischemic white matter lesions of the CNS (1.5, SD 2.2 vs. 0.5, SD 2.9, p = 0.03). In our small cohort, sNfL Z-scores correlated fairly with FOS-MSSI (Kendall's-Tau [τ] = 0.25, p = 0.01), and, interestingly with serum creatinine (τ = 0.28, p = 0.005) and estimated glomerular filtration rate (eGFR, τ =-0.28, p = 0.005). Based on these exploratory results, sNfL might provide value as a biomarker of neuroaxonal damage in FD, possibly reflecting cerebrovascular injury. Additionally, the correlation of sNfL with renal function warrants further investigation.
法布里病（FD）是一种罕见的 X 连锁溶酶体贮积症，影响多个器官系统，尤其是心脏、肾脏和中枢神经系统。神经丝轻链（NfL）已成为反映神经轴突损伤的体液生物标志物的首选候选物。我们旨在评估其在 FD 的诊断和监测工具中的添加。使用 Simoa©技术测量 50 名 FD 患者（PwFD）和 30 名健康对照者（HC）的血清 NfL 浓度（sNfL），并计算年龄和体重指数调整后的 Z 分数。此外，使用包含临床和辅助检查参数的 FOS-MSSI（法布里结局研究-美因茨严重程度评分指数）测量 PwFD 的临床疾病严重程度。PwFD 的 sNfL Z 分数高于 HC（PwFD：1.12[SD 1.5]，HC：0.01[SD 1.2]，p<0.001）。在 PwFD 中，男性的 sNfL Z 分数高于女性（1.75[SD 1.5]比 0.73[SD 1.4]）。重要的是，sNfL Z 分数在 CNS 缺血性白质病变的 PwFD 中升高（1.5，SD 2.2 比 0.5，SD 2.9，p=0.03）。在我们的小队列中，sNfL Z 分数与 FOS-MSSI 相当相关（Kendall's-Tau[τ]=0.25，p=0.01），并且与血清肌酐（τ=0.28，p=0.005）和估计肾小球滤过率（eGFR，τ=-0.28，p=0.005）相关。基于这些探索性结果，sNfL 可能作为 FD 神经轴突损伤的生物标志物具有价值，可能反映脑血管损伤。此外，sNfL 与肾功能的相关性值得进一步研究。
