Serum biomarkers in primary mitochondrial disorders.

Area of Science:

• Biochemistry
• Neurology
• Genetics

Background:

• Primary mitochondrial disorders are complex genetic conditions affecting multiple organ systems.
• Accurate diagnosis is crucial for effective management and treatment.
• Novel biomarkers are needed to improve diagnostic accuracy and monitoring.

Purpose of the Study:

• To evaluate the diagnostic utility of serum neurofilament light chain (NfL), fibroblast growth factor 21 (FGF21), and growth and differentiation factor 15 (GDF15) in primary mitochondrial disorders.
• To determine the correlation of these biomarkers with specific clinical manifestations, such as central nervous system involvement and myopathy.

Main Methods:

• Serum levels of NfL, FGF21, and GDF15 were measured in 26 patients with genetically confirmed mitochondrial disease.
• NfL was quantified using the Simoa assay, while FGF21 and GDF15 were measured by enzyme-linked immunosorbent assay.
• Biomarker levels were analyzed in relation to genetic mutations and clinical phenotypes, including neurological and muscular involvement.

Main Results:

• Elevated NfL levels were observed in patients with central nervous system involvement, particularly those with the m.3242A>G mutation and epilepsy.
• Higher FGF21 and GDF15 levels were associated with prominent myopathy, such as in patients with single mitochondrial DNA deletions.
• NfL levels correlated with the extent of ongoing cellular damage, suggesting potential prognostic value.

Conclusions:

• The combination of NfL, FGF21, and GDF15 shows promise as a diagnostic tool for mitochondrial diseases.
• FGF21 and GDF15 are indicators of muscle involvement, whereas NfL serves as a specific marker for central nervous system involvement.
• Monitoring NfL levels may offer prognostic insights and a method for tracking disease activity in mitochondrial disorders.