Evaluation of Serum FGF21 Levels in Patients with Mitochondrial Aminoacyl-tRNA Synthetase Deficiency

Fibroblast growth factor 21 (FGF21), a pleiotropic hormone, is a significant modulator of energy homeostasis. We evaluated serum FGF21 levels in patients with a deficiency of mitochondrial aminoacyl t-RNA synthetase (aARSs). Six patients with mitochondrial aminoacyl tRNA synthetase deficiency and twelve healthy volunteers were included in this study. Whole-exome sequencing was used for molecular diagnosis. Serum FGF21 levels in the case group and healthy volunteers were analyzed using the enzyme-linked immunosorbent assay. Exome sequencing test revealed nine different pathogenic variants in the AARS2, EARS2, DARS2, SARS2, and WARS2 genes. A statistically significant difference was found between the serum FGF21 levels of the case and control groups: case group (n = 6), 882.49 ± 923.60 pg/mL; control group (n = 12), 20.89 ± 2.63 pg/mL (p < 0.001). The area under the ROC Curve for FGF21 in the differential diagnosis of mitochondrial aminoacyl-tRNA Synthetase Deficiency was 0.933 (0.786-0.962). Sensitivity and Specificity 100%, Positive and Negative Predicted Value 100% were found for FGF21 >27.4 pg/mL cut-off value. Assessment of FGF 21 levels as an indicator of mitochondrial damage in mt-aARS deficiency may provide insight into the level of damage. Investigating the biochemical mechanisms underlying the varying levels of damage caused by different aminoacyl tRNA synthetases is crucial for elucidating clinical heterogeneity.