Mitochondrial Diagnoses From Skin Tests

Combining functional laboratory assays with genetic sequencing could help resolve uncertain findings and improve diagnosis of inherited mitochondrial disorders

October 27, 2026
2 min

The Pathologist

Objective:

To assess whether combined functional tests on skin fibroblasts can help identify mitochondrial dysfunction, particularly when genomic sequencing is inconclusive.

Approach:

Study samples: Researchers tested fibroblast cell lines from 204 patients with genetically confirmed mitochondrial disease, 51 healthy controls, and 53 patients with other diagnoses.
Testing: The approach combined enzyme activity assays and tests of mitochondrial performance inside cells, with targeted protein measurements where appropriate.

Key Findings:

The combined tests had 76% sensitivity and 93% specificity.
Each of the three principal assays alone had sensitivity of 40% to 49%.
Performance was strongest for disorders affecting individual respiratory chain complexes, mitochondrial protein production, and essential metabolic cofactors.
Sensitivity was lower for some mitochondrial DNA disorders, particularly those affecting DNA maintenance.

Interpretation:

The findings support using complementary fibroblast functional tests alongside genomic sequencing when genetic results are uncertain or inconclusive. A normal fibroblast result does not exclude mitochondrial disease.

Limitations:

The study tested samples from patients with established diagnoses rather than prospectively evaluating an undiagnosed population.
Test performance varied by disease category.