Koene Saskia, de Laat Paul, van Tienoven Doorlène H, Weijers Gert, Vriens Dennis, Sweep Fred C G J, Timmermans Janneke, Kapusta Livia, Janssen Mirian C H, Smeitink Jan A M
Department of Pediatrics, Nijmegen Centre for Mitochondrial Disorders, Amalia Children's Hospital, Radboudumc, Geert Grooteplein 10, 9101, 6500 HB, Nijmegen, The Netherlands.
Department of Laboratory Medicine, Radboudumc, Nijmegen, The Netherlands.
JIMD Rep. 2015;24:69-81. doi: 10.1007/8904_2015_436. Epub 2015 May 13.
In this observational cohort study, we examined the prognostic value of growth and differentiation factor 15 (GDF15) in indicating and monitoring general mitochondrial disease severity and progression in adult carriers of the m.3243A>G mutation.Ninety-seven adult carriers of the m.3243A>G mutation were included in this study. The Newcastle mitochondrial disease adult scale was used for rating mitochondrial disease severity. In parallel, blood was drawn for GDF15 analysis by ELISA. Forty-nine carriers were included in a follow-up study. In a small subset of subjects of whom an echocardiogram was available from general patient care, myocardial deformation was assessed using two-dimensional speckle-tracking strain analysis.A moderate positive correlation was found between the concentration of GDF15 and disease severity (r = 0.59; p < 0.001). The concentration of serum GDF15 was higher in m.3243A>G carriers with diabetes mellitus, cardiomyopathy, and renal abnormalities. After a 2-year follow-up, no significant correlation was found between the change in disease severity and the change in the concentration of GDF15 or between the GDF15 level at the first assessment and the change in disease severity. In the subcohort of patients of whom an echocardiogram was available, the concentration of GDF15 correlated moderately to longitudinal global strain (r = 0.55; p = 0.006; n = 23) but not to circumferential or radial strain.Our results indicate that serum GDF15 is not a strong surrogate marker for general mitochondrial disease severity. Its value in indicating myocardial deformation should be confirmed in a prospective longitudinal study.
在这项观察性队列研究中，我们检测了生长分化因子15（GDF15）在指示和监测m.3243A>G突变成年携带者的一般线粒体疾病严重程度及病情进展方面的预后价值。本研究纳入了97名m.3243A>G突变的成年携带者。采用纽卡斯尔线粒体疾病成人量表对线粒体疾病严重程度进行评分。同时，采集血液通过酶联免疫吸附测定法（ELISA）分析GDF15。49名携带者纳入随访研究。在一小部分有普通患者护理超声心动图的受试者中，使用二维斑点追踪应变分析评估心肌变形。发现GDF15浓度与疾病严重程度之间存在中度正相关（r = 0.59；p < 0.001）。患有糖尿病、心肌病和肾脏异常的m.3243A>G携带者血清GDF15浓度更高。经过2年随访，未发现疾病严重程度变化与GDF15浓度变化之间或首次评估时的GDF15水平与疾病严重程度变化之间存在显著相关性。在有超声心动图的患者亚组中，GDF浓度与纵向整体应变存在中度相关性（r = 0.55；p = 0.006；n = 23），但与圆周应变或径向应变无关。我们的结果表明，血清GDF15并非一般线粒体疾病严重程度的有力替代标志物。其在指示心肌变形方面的价值应在前瞻性纵向研究中得到证实。
