Varhaug Kristin N, Hikmat Omar, Nakkestad Hanne Linda, Vedeler Christian A, Bindoff Laurence A
Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Brain Commun. 2021 Jan 4;3(1):fcaa222. doi: 10.1093/braincomms/fcaa222. eCollection 2021.
The aim of this study was to explore the utility of the serum biomarkers neurofilament light chain, fibroblast growth factor 21 and growth and differentiation factor 15 in diagnosing primary mitochondrial disorders. We measured serum neurofilament light chain, fibroblast growth factor 21 and growth and differentiation factor 15 in 26 patients with a genetically proven mitochondrial disease. Fibroblast growth factor 21 and growth and differentiation factor 15 were measured by enzyme-linked immunosorbent assay and neurofilament light chain with the Simoa assay. Neurofilament light chain was highest in patients with multi-systemic involvement that included the central nervous system such as those with the m.3242A>G mutation. Mean neurofilament light chain was also highest in patients with epilepsy versus those without [49.74 pg/ml versus 19.7 pg/ml ( = 0.015)], whereas fibroblast growth factor 21 and growth and differentiation factor 15 levels were highest in patients with prominent myopathy, such as those with single-mitochondrial DNA deletion. Our results suggest that the combination of neurofilament light chain, fibroblast growth factor 21 and growth and differentiation factor 15 is useful in the diagnostic evaluation of mitochondrial disease. Growth and differentiation factor 15 and fibroblast growth factor 21 identify those with muscle involvement, whereas neurofilament light chain is a clear marker for central nervous system involvement independent of underlying mitochondrial pathology. Levels of neurofilament light chain appear to correlate with the degree of ongoing damage suggesting, therefore, that monitoring neurofilament light chain levels may provide prognostic information and a way of monitoring disease activity.
本研究的目的是探讨血清生物标志物神经丝轻链、成纤维细胞生长因子21和生长分化因子15在诊断原发性线粒体疾病中的效用。我们检测了26例经基因证实的线粒体疾病患者的血清神经丝轻链、成纤维细胞生长因子21和生长分化因子15。成纤维细胞生长因子21和生长分化因子15采用酶联免疫吸附测定法检测，神经丝轻链采用单分子阵列免疫检测法检测。在包括中枢神经系统受累的多系统受累患者中，如携带m.3242A>G突变的患者，神经丝轻链水平最高。癫痫患者的平均神经丝轻链水平也高于无癫痫患者[49.74 pg/ml对19.7 pg/ml（=0.015）]，而成纤维细胞生长因子21和生长分化因子15水平在以明显肌病为特征的患者中最高，如那些存在单一线粒体DNA缺失的患者。我们的结果表明，神经丝轻链、成纤维细胞生长因子21和生长分化因子15联合使用有助于线粒体疾病的诊断评估。生长分化因子15和成纤维细胞生长因子21可识别有肌肉受累的患者，而神经丝轻链是中枢神经系统受累的明确标志物，与潜在的线粒体病理无关。神经丝轻链水平似乎与持续损伤程度相关，因此，监测神经丝轻链水平可能提供预后信息以及监测疾病活动的方法。
