Glycogen Storage Diseases and ME/CFS

mariovitali

mariovitali

Senior Member (Voting Rights)
I decided to start this thread based on the latest findings of the Whole Genome Sequencing webinar from SolveCFS.

During the seminar a slide was shown related to Glycogen Storage Diseases -there are 14 types- and a specific mention was about GSD Type 13 for Enolase beta.

I decided to start looking at the cohort that i have and found one individual -out of 74 total- who is mainly active on Phoenix Rising.

I am also cc'ing @wigglethemouse for any checks on this. The SNP is rs1801175, with risk ='T' and MAF = 0.00058.

I will continue adding any results here. From what i see so far, not many SNPs are being found on GSD in 23andme chips.
 
According to gnomAd the rsID you mention rs1801175 is predicted to be deleterious
https://gnomad.broadinstitute.org/variant/17-41055964-C-T

According to ClinVar rs1801175 it is associated with Glycogen storage disease type 1
https://www.ncbi.nlm.nih.gov/clinvar/variation/11998/

Glycogen storage disease type 1 details (autosomal recessive)
https://rarediseases.org/rare-diseases/glycogen-storage-disease-type-i/

My 23andme shows PYGL rs35026927 a rare variant MAF = 0.004 with predicted deletion and associated with Glycogen storage disease type 6. However I only have one variant at this rsID and the disease normally requires 2 = autosomal recessive. But I do wonder if you have ME, does having an autosomal dominant variation make ME more severe?

The genes of interest for Glycogen storage disease are
AGL - GSD 3
ALDOA - GSD 12
ENO3 - GSD 13
G6PC - GSD 1
GAA - GSD 2
GBE1 - GSD 4
GYG1 - GSD 15
GYS1 - GSD 0
GYS2 - GSD 0
LDHA - GSD 11
PFKM - GSD7
PGAM2 - GSD 6, GSD 10
PHKA1 - GSD 9
PHKA2 - GSD 9
PHKB - GSD 9
PHKG2 - GSD 9
PYGL - GSD 6
PYGM - GSD5
SLC37A4 - GSD 1

EDIT : Updated the gene list per slide from recent Solve webinar on genetics and corrected typos
 
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slightly off topic - i wish it was easier for people to check their own genetic data against possible ME triggers/exacerbators.

there are some websites that assist - eg Livewello - but still necessary for each person to write/run multiple reports (eg 19 different genes mentioned above), adjust for hidden RS (eg 23andMe disguise pathogenic variants using a different code), adjust for forward vs backward reporting, then read the detailed clinvar info to try to understand which variants might be relevant to our own personal health.

i know it's probably impossible at the moment, but if this process was easier, more people could participate, and we'd have better data.
 
mariovitali said:
@wigglethemouse

I just got a full genome from an ME patient and found the following :


PHKA2 - rs61733281 MAF=0.66% , Risk T


It is listed as benign , could you comment please?
Click to expand...
@mariovitali Disclaimer : I'm not much of an expert. Just teaching myself as I go along (thank you Klimas paper and open data)

According to gnomAd the rsID rs1801175 is not showing any predicted issues
https://gnomad.broadinstitute.org/variant/X-18926099-C-T

It has a CADD score of 4.462, not particularly high (search Chr X, position 18926099 C>T). By way of comparison rs1801175 in the first post is 32 which could be significant for rs1801175
https://cadd.gs.washington.edu/snv

Both copies of the gene really need to have mutations in GSD type 1 to be really concerned.
https://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-i#inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.
Click to expand...

However if one of the copies has a loss of function like in the first post then it's not clear what effect that would have given that ME is hypometabolomic (it seems from metabolomic studies that liver pathways are significantly affected so who knows how that affects glycogen stores in the liver). Could it possibly make your ME worse if you don't have regular meals - that's a question I have?
 
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