Accuracy of FGF-21 and GDF-15 for the diagnosis of mitochondrial disorders: A meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of diagnostic accuracy studies.
PubMed 32585080 · doi:10.1002/acn3.51104
What was done
A systematic review and meta-analysis searched PubMed, EMBASE, MEDLINE, Web of Science, and the Cochrane Library up to January 1, 2020, to evaluate the diagnostic accuracy of fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) for mitochondrial diseases (MDs). Two independent reviewers extracted data to determine pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios (DORs), and summary receiver operating characteristic (SROC) curves across 8 included studies comprising 1,563 participants.
What was found
Eight studies were included (5 assessing FGF-21 across 718 participants; 7 assessing GDF-15 across 845 participants): - FGF-21: Pooled sensitivity was 0.71 (95% CI 0.53 to 0.84), specificity was 0.88 (95% CI 0.82 to 0.93), DOR was 18 (95% CI 6 to 54), and SROC area was 0.90 (95% CI 0.87 to 0.92). - GDF-15: Pooled sensitivity was 0.83 (95% CI 0.65 to 0.92), specificity was 0.92 (95% CI 0.84 to 0.96), DOR was 52 (95% CI 13 to 205), and SROC area was 0.94 (95% CI 0.92 to 0.96).
Why it matters
Diagnosing mitochondrial disorders is challenging due to highly heterogeneous clinical presentations. This synthesis indicates that serum GDF-15 provides superior overall diagnostic accuracy compared to FGF-21, supporting its utility as a primary circulating biomarker.
Limits
The total evidence base is small (8 studies total), with wide confidence intervals particularly around sensitivity and diagnostic odds ratios. The abstract does not report biomarker cutoffs, disease subtypes, reference standard definitions, or whether head-to-head comparisons were performed within the same cohorts.