Corticosteroid binding globulin deficiency

[Inara]

I've just realized there was a thread discussing a paper about corticosteroid-binding-globulin deficiency:
https://www.s4me.info/threads/revie...s-related-disorders-2014-marathe-torpey.8308/

I (re-)discovered that thread after I decided to post this thread.

Corticosteroid-binding globulin deficiency is a genetic disorder characterized by extreme tiredness (fatigue), particularly after physical exertion, and low blood pressure (hypotension).[1][2]Corticosteroid-binding globulin (CBG) is a protein primarily produced in the liver that attaches to cortisol, a hormone with numerous functions, including maintaining blood sugar levels, protecting the body from stress, and suppressing inflammation. When cortisol is needed in the body, CBG delivers the cortisol where it is needed and releases it.[1][3]

Signs and symptoms of CBG deficiency vary. While some individuals may experience no symptoms, others are found to have a fatty liver and chronic pain. Some people with CBG deficiency also have chronic fatigue syndrome. CGB deficiency is caused by mutations in the SERPINA6 gene. The SERPINA6 gene is commonly also referred to as the CBG gene. Both autosomal dominant and autosomal recessive inheritance have been reported.[1][2] While there is still no cure, treatment options will depend on the type and severity of symptoms present and may involve several specialists.

https://rarediseases.info.nih.gov/diseases/13101/corticosteroid-binding-globulin-deficiency

I am not entirely sure which definition for CFS they use, but I think it's "chronic fatigue", including fast fatiguability (also of the muscles); they also describe something that might be PEM. CBG researchers don't view CBG deficiency as psychological, although some have a psychiatric background (because they learnt that "fatigue" is not always depression).

It was found and confirmed that I (besides another rare mutation in ITPR3 which is being researched right now) have a known, rare gene variant of SERPINA6 which might explain part of my symptoms. Since CBGD is very rare, only a small portion of pwME might have CBGD (and maybe not solely because it doesn't explain ME symptoms entirely...). I also learnt that neuropathies don't seem to occurr in CBGD, which are not uncommon in ME (and I have them, too).

I don't know much about treatment options but they don't seem to be awesome. So the worth of this diagnosis to me is to have one (objective) cause for some of my symptoms.

 

[Amw66]

I've just realized there was a thread discussing a paper about corticosteroid-binding-globulin deficiency:
https://www.s4me.info/threads/revie...s-related-disorders-2014-marathe-torpey.8308/

I (re-)discovered that thread after I decided to post this thread.


https://rarediseases.info.nih.gov/diseases/13101/corticosteroid-binding-globulin-deficiency

I am not entirely sure which definition for CFS they use, but I think it's "chronic fatigue", including fast fatiguability (also of the muscles); they also describe something that might be PEM. CBG researchers don't view CBG deficiency as psychological, although some have a psychiatric background (because they learnt that "fatigue" is not always depression).

It was found and confirmed that I (besides another rare mutation in ITPR3 which is being researched right now) have a known, rare gene variant of SERPINA6 which might explain part of my symptoms. Since CBGD is very rare, only a small portion of pwME might have CBGD (and maybe not solely because it doesn't explain ME symptoms entirely...). I also learnt that neuropathies don't seem to occurr in CBGD, which are not uncommon in ME (and I have them, too).

I don't know much about treatment options but they don't seem to be awesome. So the worth of this diagnosis to me is to have one (objective) cause for some of my symptoms.

Interesting.
How low does cortisol (and blood pressure) have to be for this to be considered?

 

[Inara]

When lying I have a BP around 90/50 - 100/60, pulse 40-60. When upright, though, BP rises to normal and pulse up to 140 (but I have hyperadrenergic POTS). My cortisol is low-normal (low in the evening). If I understood correctly, in CBGD cortisol is often low-normal, not low.

One can speculate about the connection "hyperadrenergic POTS - CBGD - low BP", but it is not researched.

One of the SERPINA6 variants I have is known and classified as pathogenic. I don't know 100% when the experts decide that a variant leads to CBGD (some variants seem to lead to CBGD in some, and in others the same variants don't, and the reason for this is not fully understood I think), but they determined lots of lab values and I trust they know what they're doing.