Accuracy of FGF‐21 and GDF‐15 for the diagnosis of mitochondrial disorders: A meta‐analysis

OBJECTIVE: Given their diverse phenotypes, mitochondrial diseases (MDs) are often difficult to diagnose. Fibroblast growth factor 21 (FGF‐21) and growth differentiation factor 15 (GDF‐15) represent promising biomarkers for MD diagnosis. Herein we conducted a meta‐analysis to compare their diagnostic accuracy for MDs. METHODS: We comprehensively searched PubMed, EMBASE, MEDLINE, the Web of Science, and Cochrane Library up to 1 January 2020. Data were analyzed by two independent reviewers. We obtained the sensitivity and specificity, positive and negative likelihood ratios (LR+ and LR‐), diagnostic odds ratios (DORs) and summary receiver operating characteristic (SROC) curves of each diagnostic method. RESULTS: Eight randomized controlled trials (RCTs) including 1563 participants (five encompassing 718 FGF‐21 assessments; seven encompassing 845 participants for GDF‐15) were included. Pooled sensitivity, specificity, DOR and SROC of FGF‐21 were 0.71 (95% CI 0.53, 0.84), 0.88(95% CI 0.82, 0.93), 18 (95% CI 6, 54), 0.90 (95% CI 0.87, 0.92), respectively, which were lower than GDF‐15 values; 0.83 (95% CI 0.65, 0.92), 0.92 (95% CI 0.84, 0.96), 52 (95% CI 13, 205), 0.94 (95% CI 0.92, 0.96). INTERPRETATION: FGF‐21 and GDF‐15 showed acceptable sensitivity and high specificity. Of the biomarkers, GDF‐15 had the highest diagnostic accuracy.