Suomalainen · Handbook of clinical neurology 2023 · narrative review · n=?

Blood biomarkers of mitochondrial disease-One for all or all for one?

Level 5 - mechanism / opinion, no new human data

Narrative review without systematic search or meta-analytic methodology.

PubMed 36813317 · doi:10.1016/B978-0-12-821751-1.00006-3 · record verified 2026-08-26

What was done

The author conducted a narrative review summarizing the development and clinical application of blood-based biomarkers for diagnosing and monitoring mitochondrial diseases over the past decade. The review contrasts conventional biomarkers (lactate, pyruvate, alanine) with newer metabokines (FGF21, GDF15), cofactors such as NAD+ forms, and multi-metabolite or metabolomic profiling panels.

What was found

The abstract reports no quantitative metrics or diagnostic performance statistics (such as sensitivity, specificity, or receiver operating characteristic values). Qualitatively, the review notes that FGF21 and GDF15 serve as systemic signals of the mitochondrial integrated stress response and demonstrate superior sensitivity and specificity compared to lactate, pyruvate, and alanine in muscle-manifesting mitochondrial disorders. It also identifies secondary metabolic alterations, including NAD+ depletion, as candidate biomarkers and therapeutic targets.

Why it matters

Mitochondrial diseases present with broad clinical heterogeneity, making diagnosis challenging. Newer circulating metabokines and metabolomic panels improve diagnostic prioritization and provide tools for monitoring disease progression and therapeutic response in clinical trials.

Limits

No quantitative performance data or sample sizes are provided in the abstract. As a narrative review, it lacks a systematic literature search protocol and risk-of-bias evaluation. Furthermore, biomarker utility remains highly tissue- and phenotype-specific, requiring tailored panels for different clinical presentations.

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