Li Yi, Li Shengrui, Qiu Yinfeng, Zhou Maobin, Chen Min, Hu Yue, Hong Siqi, Jiang Li, Guo Yi
Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China.
National Clinical Research Center for Child Health and Disorders, Chongqing, China.
Front Pediatr. 2022 Apr 14;10:851534. doi: 10.3389/fped.2022.851534. eCollection 2022.
Primary mitochondrial disorders (PMDs) are a diagnostic challenge for paediatricians, and identification of reliable and easily measurable biomarkers has become a high priority. This study aimed to investigate the role of serum fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) in children with PMDs.
We analysed serum FGF21 and GDF15 concentrations by enzyme-linked immunosorbent assay (ELISA) in children with PMDs, patients with non-mitochondrial neuromuscular disorders (NMDs), and aged-matched healthy children, and compared them with serum lactate and ratio of lactate and pyruvate (L/P). We also evaluated correlations between these biomarkers and the phenotype, genotype, and severity of PMDs.
The median serum GDF15 and FGF21 concentrations were significantly elevated in fifty-one patients with PMDs (919.46 pg/ml and 281.3 pg/ml) compared with those of thirty patients with NMDs (294.86 pg/ml and 140.51 pg/ml, both < 0.05) and fifty healthy controls (221.21 pg/ml and 85.02 pg/ml, both < 0.05). The area under the curve of GDF15 for the diagnosis of PMDs was 0.891, which was higher than that of the other biomarkers, including FGF21 (0.814), lactate (0.863) and L/P ratio (0.671). Calculated by the maximum Youden index, the critical value of GDF15 was 606.369 pg/ml, and corresponding sensitivity and specificity were 74.5and 100%. In the PMD group, FGF21 was significantly correlated with International Paediatric Mitochondrial Disease Scale (IPMDS) score. The levels of GDF15 and FGF21 were positively correlated with age, critical illness condition, and multisystem involvement but were not correlated with syndromic/non-syndromic PMDs, different mitochondrial syndromes, nuclear DNA/mitochondrial DNA pathogenic variants, gene functions, or different organ/system involvement.
Regardless of clinical phenotype and genotype, circulating GDF15 and FGF21 are reliable biomarkers for children with PMDs. GDF15 can serve as a screening biomarker for diagnosis, and FGF21 can serve as a severity biomarker for monitoring.
原发性线粒体疾病（PMDs）对儿科医生来说是一项诊断挑战，识别可靠且易于测量的生物标志物已成为当务之急。本研究旨在探讨血清成纤维细胞生长因子21（FGF21）和生长分化因子15（GDF15）在PMDs患儿中的作用。
我们采用酶联免疫吸附测定（ELISA）法分析了PMDs患儿、非线粒体神经肌肉疾病（NMDs）患者及年龄匹配的健康儿童血清中FGF21和GDF15的浓度，并将其与血清乳酸及乳酸与丙酮酸比值（L/P）进行比较。我们还评估了这些生物标志物与PMDs的表型、基因型及严重程度之间的相关性。
51例PMDs患儿血清GDF15和FGF21浓度中位数显著高于3０例NMDs患者（分别为919.46 pg/ml和281.3 pg/ml，均P<0.05）及50例健康对照（分别为221.21 pg/ml和85.02 pg/ml，均P<0.05）。GDF15诊断PMDs的曲线下面积为0.891，高于其他生物标志物，包括FGF21（0.814）、乳酸（0.863）和L/P比值（0.671）。按最大约登指数计算，GDF15的临界值为606.369 pg/ml，相应的敏感度和特异度分别为74.5%和100%。在PMD组中，FGF21与国际儿科线粒体疾病量表（IPMDS）评分显著相关。GDF15和FGF21水平与年龄、危重症状态及多系统受累呈正相关，但与综合征性/非综合征性PMDs、不同线粒体综合征、核DNA/线粒体DNA致病变异、基因功能或不同器官/系统受累无关。
无论临床表型和基因型如何，循环GDF15和FGF21都是PMDs患儿可靠的生物标志物。GDF15可作为诊断的筛查生物标志物，FGF21可作为监测的严重程度生物标志物。
