The aim of this study was to compare the value of serum biomarkers, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), with histological analysis of muscle in the diagnosis of mitochondrial disease. We collected 194 serum samples from patients with a suspected or known mitochondrial disease. Biomarkers were analyzed blinded using enzyme‐labeled immunosorbent assay. Clinical data were collected using a structured questionnaire. Only 39% of patients with genetically verified mitochondrial disease had mitochondrial pathology in their muscle histology. In contrast, biomarkers were elevated in 62% of patients with genetically verified mitochondrial disease. Those with both biomarkers elevated had a muscle manifesting disorder and a defect affecting mitochondrial DNA expression. If at least one of the biomarkers was induced and the patient had a myopathic disease, a mitochondrial DNA expression disease was the cause with 94% probability. Among patients with biomarker analysis and muscle biopsy taken <12 months apart, a mitochondrial disorder would have been identified in 70% with analysis of FGF21 and GDF15 compared to 50% of patients whom could have been identified with muscle biopsy alone. Muscle findings were nondiagnostic in 72% (children) and 45% (adults). Induction of FGF21 and GDF15 suggest a mitochondrial etiology as an underlying cause of a muscle manifesting disease. Normal biomarker values do not, however, rule out a mitochondrial disorder, especially if the disease does not manifest in muscle. We suggest that FGF21 and GDF15 together should be first‐line diagnostic investigations in mitochondrial disease complementing muscle biopsy.

中文翻译：

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与肌肉样本相比，血清生物标志物 FGF21 和 GDF15 在线粒体疾病中的诊断价值

本研究的目的是比较血清生物标志物、成纤维细胞生长因子 21 (FGF21) 和生长分化因子 15 (GDF15) 与肌肉组织学分析在线粒体疾病诊断中的价值。我们收集了 194 份疑似或已知线粒体疾病患者的血清样本。使用酶标免疫吸附试验对生物标志物进行盲法分析。使用结构化问卷收集临床数据。只有 39% 的遗传证实的线粒体疾病患者在其肌肉组织学中具有线粒体病理学。相比之下，62% 的遗传证实的线粒体疾病患者的生物标志物升高。那些两个生物标志物都升高的人有肌肉表现障碍和影响线粒体 DNA 表达的缺陷。如果诱导了至少一种生物标志物并且患者患有肌病，则线粒体 DNA 表达疾病是病因，概率为 94%。在生物标志物分析和肌肉活检相隔 <12 个月的患者中，通过分析 FGF21 和 GDF15 可以确定 70% 的患者患有线粒体疾病，而仅通过肌肉活检可以确定为 50% 的患者。72%（儿童）和 45%（成人）的肌肉检查结果无法诊断。FGF21 和 GDF15 的诱导表明线粒体病因是肌肉表现疾病的潜在原因。然而，正常的生物标志物值并不能排除线粒体疾病，特别是如果该疾病没有在肌肉中表现出来。