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

## TL;DR

This study found that serum FGF21 levels are significantly higher in patients with mitochondrial aminoacyl-tRNA synthetase deficiency compared to healthy individuals, suggesting a potential biomarker for the condition.

## Contribution

The study identifies elevated serum FGF21 as a potential diagnostic biomarker for mitochondrial aminoacyl-tRNA synthetase deficiency.

## Key findings

- Serum FGF21 levels in patients with mt-aARS deficiency were significantly higher than in healthy controls (p < 0.001).
- FGF21 showed 100% sensitivity and specificity for diagnosing mt-aARS deficiency with a cut-off of >27.4 pg/mL.
- FGF21 levels may reflect the degree of mitochondrial damage in mt-aARS deficiency.

## Abstract

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-tRNA synthetase (mt-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 1.000 (0.813–1.000). Sensitivity and specificity were 100%, and positive and negative predictive values were also 100% for an FGF21 cut-off value > 27.4 pg/mL. Assessment of FGF 21 levels as an indicator of mitochondrial damage in mt-aARSs deficiency may provide insight into the level of damage. Investigation of the biochemical mechanisms underlying the different levels of damage caused by different aminoacyl tRNA synthetases will be important in terms of elucidating clinical heterogeneity.