5 Key Takeaways

• 1

  Genomic sequencing is the recommended first-line investigation for suspected primary mitochondrial disease but yields a diagnosis in only 50% to 65% of cases.

• 2

  Researchers evaluated skin fibroblasts from 204 patients with genetically confirmed mitochondrial disease, 51 healthy controls, and 53 patients with other diagnoses.

• 3

  Combining enzyme activity, mitochondrial performance, and targeted protein assays detected mitochondrial dysfunction with 76% sensitivity and 93% specificity.

• 4

  The combined approach performed particularly well for disorders affecting respiratory chain complexes, mitochondrial protein production, and essential metabolic cofactors.

• 5

  Sensitivity was lower for some mitochondrial DNA disorders, especially those affecting DNA maintenance, so a normal fibroblast result cannot exclude mitochondrial disease.