Thus, the overall positive and negative predictive values were not acceptable for these measurements to be used as diagnostic tests for mitochondrial diseases (FGF-21 positive predictive value [PPV] = 34%, negative predictive value [NPV] = 73%; GDF-15 PPV = 47%, NPV = 28%).
Serum fibroblast growth factor 21 (FGF-21) is a biomarker for mitochondrial disease and could be a candidate to monitor mitochondrial function in the deleterious course of disease.
In the present review, a literature research, using PubMed database about the reliability of FGF-21 as a biomarker for mitochondrial disorders and its comparison with GDF-15 has been performed.
Fibroblast growth factor-21 (FGF21) levels are elevated in patients with primary mitochondrial disorders but have not been studied in patients with inborn errors of metabolism (IEM) known to have secondary mitochondrial dysfunction.
The area under the curve of growth differentiation factor 15 for the diagnosis of muscle-manifesting mitochondrial diseases was 0.999, in comparison with those area under the curves of the other biomarkers including fibroblast growth factor 21 (0.935, p < 0.01), lactate (0.845 for p < 0.001), and creatine kinase (0.575, p < 0.001).
Mitochondrial myopathy (MM) is the most common manifestation of adult-onset mitochondrial disease and shows a multifaceted tissue-specific stress response: (1) transcriptional response, including metabolic cytokines FGF21 and GDF15; (2) remodeling of one-carbon metabolism; and (3) mitochondrial unfolded protein response.
Other MD patients harbouring mtDNA point mutations (<i>n</i> = 40) or mutations in other autosomal genes (<i>n</i> = 7) and those with partially characterised MD had lower FGF-21 levels.
Conclusions FGF21 elevation may be associated with certain types of mitochondrial disease, and it is influenced by insulin resistance.Muscle Nerve 55: 564-569, 2017.
Although this study is limited, we conclude that urine organic acid test in combination with plasma FGF21 determination are valuable tools in the diagnosis of mitochondrial diseases.
S-FGF21 is a specific biomarker for muscle-manifesting defects of mitochondrial translation, including mitochondrial transfer-RNA mutations and primary and secondary mtDNA deletions, the most common causes of mitochondrial disease.
Use of new techniques such as the measurement of serum FGF-21 levels and next-generation-sequencing protocols should simplify the diagnosis of mitochondrial disease.