mtDNA deletion [...] with < 10 % heteroplasmy in muscle and isolated complex-V dysfunction misinterpreted as [CFS] over 21-years, 2025, Finsterer+

mtDNA deletion m.8753_16566 with < 10 % heteroplasmy in muscle and isolated complex-V dysfunction misinterpreted as chronic fatigue syndrome over 21-years

Josef Finsterer, Ana C. Fiorini, Fulvio A. Scorza, Carla A. Scorza

[No abstract]

Link | PDF (Clinics) [Open Access]

 

[5] is: An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients (Missailidis et al, 2020, Int. J. Mol. Sci.) (S4ME link)

 

Interesting to see how this is framed as a "misinterpretation" or "mimicking" of ME/CFS, when very clearly the patient has ME/CFS (qualifying under the usual syndromic definitions, as quoted by Forestglip above). Why not simply speculate that this could be a potential cause for ME/CFS?

Also fascinating that she would have had muscle biopsies, endocardial biopsy, NK function tests and CPET, yet has not had a simple brain MRI despite "Since the age of 34, she had recurrent strokelike symptoms".

Key points —

KSS is Kearns-Sayre Syndrome.

 

Why doesn’t the title mention ‘case report’?

 

I hope we don’t get to a point where anyone with ‘biological’ changes don’t have ME/CFS.

 

Whenever I read about people having problems with the various complexes in the mitochondrial chain I think about Hwang and WASF3. He found in his patient that WASF3 inhibited two complexes joining together to make a supercomplex, which would run more efficiently (and then detected high wasf3 in a wider group). Maybe the variation in mecfs is about different ways the chain is broken?
The only problem I have with a mitochondrial centric view of me/cfs is that I'd have guessed we would have found the problem by now if it was indeed usually in the mitochondria.

 

How easy is it to study mitochondria, and how much do we know about them? I’m assuming their functionality is highly dependent on the environment they are in - so isolating them might produce different behaviours?

 

True, ME could involve a mitochondrial problem in only a few specialized brain cells. Very hard to find that unless you know what to look for (and where). Moreover, it might not show up in autopsy samples, or even living cells without the environmental factors that lead to ME.

 

This idea of heteroplasmy could also be relevant to mecfs: you need have the genetic problem in only some of your mitochondria for symptoms to develop. It would be an obvious way to distinguish mild moderate and severe.

 

"mtDNA analysis from muscle at 46 years of age revealed the m.8753_16,566 deletion with <10 % heteroplasmy. The deletion was larger than in patients with KSS but encompassed the entire ATP6 gene associated with complex-V of the respiratory chain. An abnormal complex-V band was detected in the MitoFIND assay, indicating that the mutation was a germline mtDNA deletion"

One of our ME PhD students is looking at this gene (amongst other things)!

 

Can study them inside live samples from patients - easier or harder depending on the tissue of interest. We have done it in circulating immune cells, primary fibroblast lines and immortalised cell lines. Others have done it on immune cell subsets and muscle biopsies