DWQA QuestionsCategory: QuestionsKeratoconus and CPT-II deficiency
Doina asked 3 years ago

Hi,
I am a patient living with CPT-II deficiency, and I have a few questions regarding my diagnosis with keratoconus last year. It seems that mitochondrial dysfunction can be linked with this eye disorder, and an article suggested patients with mitochondrial disease start taking the mito cocktail to reduce reactive oxygen species that could be linked to the pathogenesis of keratoconus. Would it recommend it for cpt 2 patients specifically?
Could you please also help me clarify a few points?:

    1. If I understand well, with cpt 2 deficiency, the problem is that long chain fatty acids simply cannot enter the mitochondria. Thus, the mitochondria itself does not produce more ROS. However, I read that ROS could be increased through another mechanism: an accumulation of long-chain fatty acids can lead to increased cytokines = increased inflammation = increased ros = increased cell damage. Is there still an increase in ROS in CPT II patients?
        1. If there is an increase in ROS due to the accumulation in long-chain fatty acids in CPT II deficiency, what if I limit my long-chain fatty acid intake? Will I still have a higher concentration of free fatty acids in my blood?

       

        1. If there is an increase in ROS, does it happen only outside the mitochondria? Then, if I do take antioxidants, do they still have to enter the mitochondria, since inflammation happens OUTSIDE the mitochondria?
            1. Which antioxidants would be recommended for me?

           

           

       

       

 

2.  Do you think keratoconus can be linked with cpt 2 deficiency? I don’t have other risk factors, and it seems like the eye disorders associated with mitochondrial dysfunction are mostly droppy eyelids, and thinning of the optic nerves.
Thank you so much,
Susan

Physician
replied 3 years ago

There is no demonstrated increase in the incidence in keratoconus in FAODs. Your questions about ROS are quite timely and complicated. The bottom line is that there is very little known about the presence and/or mechanism of its development. My own research suggests that there is and that it is related to secondary dysfunction of oxidative phosphorylation. However, this hypothesis needs more research to be proven. Because standard antioxidants do not reach the mitochondrial efficiently, we are investigating a new family of mitochondrial targeted antioxidants and have published data showing that they are effective in reducing ROS in VLCAD deficient patient derived fibroblasts. More work is in progress. In the meantime I don’t recommend using antioxidants as there is little or evidence showing benefit or identifying risks. I hope this helps. Dr. Vockley