In the second part of this series, Dr. Katie Krulisky and Dr. Cristina Domínguez-González explore the most effective approach to evaluating suspected mitochondrial disease.

Show citation:

Bermejo-Guerrero L, Restrepo-Vera JL, Martin-Jimenez P, et al. Clinical Heterogeneity and Candidate Biomarkers in POLG-Related Mitochondrial Disease. Neurol Genet. 2026;12(2):e200365. Published 2026 Mar 10. doi:10.1212/NXG.0000000000200365

Show transcript:

Dr. Katie Krulisky:

This is The Neurology Minute. This is the second part of our series. I'm Katie Krulisky from the University of Utah and I'm here with Cristina Domínguez-González from the 12th of October University Hospital and its affiliated health research institute in Madrid, Spain. We've just recorded a full podcast on our paper, Clinical Heterogeneity and Candidate Biomarkers in POLG-related Mitochondrial Disease, which has been published in Neurology Genetics.

Cristina, for The Minute, what's the most practical way to work up suspected mitochondrial disease today?

Dr. Cristina Domínguez-González:

In practice, everything starts with the clinical picture. Recognizing the pattern, whether it's a combination of features or a more subtle isolated presentation, is what should first raise suspicion. From there, you decide the next step. Targeted genetic testing if the phenotype is well-defined, grow their sequencing if it is less clear or more complex.

Biomarkers can also be very helpful. GDF15, Growth Differentiation Factor 15, is markedly elevated in many mitochondrial diseases and can support the suspicion. In myopathies in particular, it is especially useful because of its high negative predictive value helping to rule out a mitochondrial cause when levels are not elevated.

And finally, muscle biopsy still has a role. It can provide important information in selected cases, particularly in adults or when genetic results are inconclusive, both for diagnosis and also to guide further studies.

Dr. Katie Krulisky:

Thank you. That's super helpful. And for more on mitochondrial diseases and POLG-related disorders, have a listen to the full neurology podcast.

Again, I'm Katie Krulisky from the University of Utah with Cristina Domínguez-González from the 12th of October University Hospital and its affiliated health research institute in Madrid, Spain.