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)

 

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

 

This is an important point that needs to be debated. I've heard that conditions like IH, CCI or even unidentified bone-infection can mimic ME/CFS. The problem is that those are treatable conditions. I've even met someone who suffered from hemochromatosis (?) or something and cried river saying that his life was now over because he had ME/CFS, and then got cured 3 years later after getting treated properly. I don't know the mitochondrial condition in this paper is treatable or not, but it apparently explains the symptoms. And the syndrome definition requires that the symptoms are not explained by other conditions.

I think it just goes to show the importance of getting diagnosed properly. There is no reason to suffer needlessly if it is treatable. That's not same thing as saying that it is not ME/CFS if it has a biological cause. ME/CFS will eventually prove to have a biological cause, I'm sure. It's just that it is not known at the moment.

 

Posted on behalf of @MSEsperanza:


I'm afraid that omission aligns well with at least one of the authors having been associated with using paper mills for publishing.

Thanks to Nick Brown https://bsky.app/profile/steamtraen.hopto.org for digging out the pubpeer comment on an unrelated paper by Finsterer:

https://pubpeer.com/publications/0122380B6FAE8AFE8625052182E72D


I thought just Finsterer's rate and variety of publications was strange, also those in the more unsuspicious journals mostly tend to be letters:

https://orcid.org/0000-0003-2839-7305

It's still possible that there is some sensible stuff in the paper, just maybe better to remain extra-skeptical in this case.