M.A.D.D. maybe your reason for cfs? (1-2% chance for Adenosine monophosphate deaminase deficiency type 1)

[linusbert]

this isnt new, i think people talked about this somewhere in the forum but not all are aware.
there are certain genetic conditions like the MADD which are rare but with 1-2% imho quite common among populations and resemble symptoms of cfs.
and there are a lot of similiar diseases in the metabolic diseases(myopathies) area.

a genetic test would reveal this, we found this for a close friend in a 23andme test.

the madd can respond to high doses of d-ribose like 10g+.
EDIT: taken from that wikipedia article:

10 grams per 100 pounds (0.2 g/kg) of body weight per day,

/EDIT

https://en.wikipedia.org/wiki/Adenosine_monophosphate_deaminase_deficiency_type_1

ma

 

[Judee]

Glad you posted about it in case there's someone here like that. How do we tell if we have it? What does it look like on 23and me?

Asking though I'm pretty sure it's not me. D-ribose put me in the ER and it was a really weird feeling because my brain could sense my heart was reacting in a very strange way...like someone running up a stairway then back down a stairway right away.

That's what my heart was doing, increasing speed, and then just as quickly decreasing speed, over and over again even with me just standing or sitting still.

 

[linusbert]

looks somewhat like this, though in this case its not homozygote.
i dont know how pathogenic heterozygote is.

23andme changes their tested genes all the time. i dont know if the current version does include this. so its not reliable.
doing WGS with a provider like nebula genomics might be beneficial, and also more expensive.

the person owning this genetics also didnt react to well to d-ribose. but not as bad as you experienced.

https://www.snpedia.com/index.php/rs17602729

 

[Hip]

To check your 23andme SNP results to see if you have the adenosine monophosphate deaminase deficiency type 1 (AMPD1) allele, note that the ID for this SNP is rs17602729, according to Wikipedia.

So on 23andme, you can find your allele for this rs17602729 SNP HERE.


According to SNPedia, in your 23andme results shown at the above link, the risk allele for AMPD1 is A / A if you are homozygous (+/+), or A / G if you are heterozygous (+/-).

Those who do not have the risk allele for AMPD1 will be G / G in their 23andme results.

These values quoted are for positive strand orientation.

23andme always report allele orientation on the positive DNA strand, whereas SNPedia may report on the positive or negative strand. In the SNPedia page linked to above, they state at the top of the page that they are reporting on the negative strand, but we want the positive strand orientation, so you have to look at the "orientation reversed" results on that SNPedia page, which are the A/A, A/G and G/G values mentioned.



Apparently myoadenylate deaminase deficiency (MADD) is the old name for this metabolic disorder; it is now called adenosine monophosphate deaminase deficiency type 1 (AMPD1).

 

[Judee]

23andme changes their tested genes all the time. i dont know if the current version does include this. so its not reliable.

Those who do not have the risk allele for AMPD1 will be G / G in their 23andme results.

Thank you both. I used the SNP number and found it on my raw data. Mine's G/G so "Normal."

Oh, well. Back to the drawing board for me.

Still glad you posted it @linusbert. Someone might be helped.

 

[datadragon]

Apparently myoadenylate deaminase deficiency (MADD) is the old name for this metabolic disorder; it is now called adenosine monophosphate deaminase deficiency type 1 (AMPD1).

Yes but AMPD is a zinc enzyme (adenosine monophosphate deaminase) so again, deficiency may not be related to genetic causes for most. https://en.wikipedia.org/wiki/Adenosine_monophosphate_deaminase_deficiency_type_1

The hydrolytic deamination of AMP to IMP and NH3 is catalysed by AMP deaminase (AMPD), a zinc enzyme that, although is distributed in most animal tissues, shows a particularly elevated activity in skeletal muscle. AMPD is present as multiple isoforms in muscle fibers.

https://link.springer.com/article/10.1007/s11010-023-04763-7
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164516/
https://link.springer.com/article/10.1007/s12210-016-0586-7

Zinc deficiency also causes delayed ATP clearance and adenosine generation https://forums.phoenixrising.me/threads/role-of-dysfunctional-glycolysis.91264/#post-2449814

In this review we report the evidence of the interaction between TnT and AMP deaminase (AMPD), a regulated zinc enzyme localized on the myofibril. In periods of intense muscular activity, a decrease in the ATP/ADP ratio, together with a decrease in the tissue pH, is the stimulus for the activation of the enzyme that deaminating AMP to IMP and NH3 displaces the myokinase reaction towards the formation of ATP.
The ability of the TnT variable N-terminal region to interact through a zinc bridge with the enzyme catalyzing the deamination of AMP to maintain a high energy charge and supply myosin ATPase with ATP could be at the base of a rapid and fine-tuned adaptation to the changes in contractile demands. the zinc-binding protein HPRG we have shown to be candidate to provide the zinc ions to stabilize the AMPD1 native conformation. Furthermore, a clear correlation between the muscle HPRG content and the level of AMPD activity was obtained from the immunological analyses of human skeletal muscle biopsies from patients with AMPD deficiency. ,

the skeletal muscle enzyme (AMPD1) is activated during exercise, when the rate of ATP utilization exceeds the potential of the cell to resynthesize ATP. Because AMP deamination displaces the equilibrium of the myokinase reaction (2 ADP = 1 ATP + 1 AMP) toward ATP resynthesis, a proposed role for AMPD1 is to alleviate the exercise-induced decrease in the ATP/ADP ratio and its inhibitory effect on muscle contraction

Taking in consideration that the N-terminus of TnT expressed in human as well as rabbit white muscle contains a zinc-binding motif, we suggest that TnT might mimic the regulatory action of the inhibitory N-terminal domain of AMPD due to the presence of a zinc ion connecting the N-terminal and C-terminal regions of the enzyme, indicating that the two proteins might physiologically associate to modulate muscle contraction and ammonia production in fast-twitching muscle under strenuous conditions.

Since the N-terminal region of fast rabbit TnT contains a putative zinc-binding motif, it could mimic the regulatory action of the AMPD1 N-terminal domain that, when present, forms a dinuclear zinc site with the C-terminal catalytic zinc and maintains the enzyme in its native conformation showing both the positive homotropic behaviour (i.e., activation by the substrate AMP) and the modulation by adenosine di- and triphosphates (i.e., activation by ADP and inhibition by ATP)

 

[Alvin2]

I used to take 5g of ribose to prevent/treat PEM. Did okay but did not give me any extra functioning. I was just as housebound.
Should it have has some effect if i have this even though it was only half the dose?

 

[Hip]

Yes but AMPD is a zinc enzyme (adenosine monophosphate deaminase) so again, deficiency may not be related to genetic causes for most. https://en.wikipedia.org/wiki/Adenosine_monophosphate_deaminase_deficiency_type_1

Bullshit. There is no suggestion in the scientific literature adenosine monophosphate deaminase deficiency is caused by anything other than genetic mutations.

 

[linusbert]

I used to take 5g of ribose to prevent/treat PEM. Did okay but did not give me any extra functioning. I was just as housebound.
Should it have has some effect if i have this even though it was only half the dose?

the following the wikipedia article says:

10 grams per 100 pounds (0.2 g/kg) of body weight per day,

so i guess its somewhere around 10-25g per day depending on your weight. also they write multiple times a day,so i guess that 10-25g dose should be split up over the day.
i am a 130kg living cadaver , would have to take 25g over the day. i am also getting diarrhea pretty fast already around a single 5g dose, so i wouldnt know how to even take that much.

also according how they explain the mechanism, it might be most effective in case energy demands exceeded regular ATP production, like when overexercising. so this might be mostly beneficial to take after overdoing it, the following days.

somewhere else i read that the body uses plain sugar to work in that pathway, but its slow and can take 48 hours. thats where d-ribose helps, as it is available almost instantly.
but its not the only thing needed to make ATP in denovo synthesis. its just the biggest bottleneck.

https://en.wikipedia.org/wiki/Adenosine_monophosphate_deaminase_deficiency_type_1#Treatment

It is important for MADD patients to maintain strength and fitness without exercising or working to exhaustion. Learning this balance may be more difficult than normally, as muscle pain and fatigue may be perceived differently from normal individuals.[19]

Symptomatic relief from the effects of MADD may sometimes be achieved by administering ribose orally at a dose of approximately 10 grams per 100 pounds (0.2 g/kg) of body weight per day, and exercise modulation as appropriate. Taken hourly, ribose provides a direct but limited source of energy for the cells. Patients with myoadenylate deaminase deficiency do not retain ribose during heavy exercise, so supplementation may be required to rebuild levels of ATP.[20][21]

Creatine monohydrate could also be helpful for AMPD patients, as it provides an alternative source of energy for anaerobic muscle tissue and was found to be helpful in the treatment of other, unrelated muscular myopathies.[22]

 

[Alvin2]

the following the wikipedia article says:

so i guess its somewhere around 10-25g per day depending on your weight. also they write multiple times a day,so i guess that 10-25g dose should be split up over the day.
i am a 130kg living cadaver , would have to take 25g over the day. i am also getting diarrhea pretty fast already around a single 5g dose, so i wouldnt know how to even take that much.

also according how they explain the mechanism, it might be most effective in case energy demands exceeded regular ATP production, like when overexercising. so this might be mostly beneficial to take after overdoing it, the following days.

somewhere else i read that the body uses plain sugar to work in that pathway, but its slow and can take 48 hours. thats where d-ribose helps, as it is available almost instantly.
but its not the only thing needed to make ATP in denovo synthesis. its just the biggest bottleneck.

https://en.wikipedia.org/wiki/Adenosine_monophosphate_deaminase_deficiency_type_1#Treatment

Much of this sounds familiar. I wish i had kept better notes when i tried it but iirc i was taking 5g twice daily but found 5g once daily was fine. But when i didn't have PEM it was not doing anything, it worked as a PEM shield/treatment. I found it took about 12 hours to work which lined up with info i had read at the time. Its also very expensive so i stopped taking it and since i don't try to PEM myself it was not helping otherwise. Though that does suggest energy deficiency is part of my condition since it would work when i overdid it and wanted faster recovery.

Creatine had no effect on me, though again i might not have dosed at the level needed for MADD. Also when i get blood tests and they test creatine its in the normal range without supplementation.
I have not gotten genetic testing, though i have been referred to a geneticist but the referral takes 18-24 months and it was only done in November.

 

[Shanti1]

Turns out I'm heterozygous:

Its hard to say how much this plays into my ME/CFS as I don't have muscle pain, cramping or weakness. Obviously, I have exercise intolerance and prolonged recovery, but I could exercise before I got ME (though capacity was always mildly reduced). I've taken ribose and creatine before (wiki article) and I felt worse with both of them. However, I haven't tried them since I cleared my Candida krusei and started valacyclovir (suppressing my EBV) and I react to somethings differently now, so I am going to try them again.

 

[linusbert]

Turns out I'm heterozygous:
View attachment 53576
Its hard to say how much this plays into my ME/CFS as I don't have muscle pain, cramping or weakness. Obviously, I have exercise intolerance and prolonged recovery, but I could exercise before I got ME (though capacity was always mildly reduced). I've taken ribose and creatine before (wiki article) and I felt worse with both of them. However, I haven't tried them since I cleared my Candida krusei and started valacyclovir (suppressing my EBV) and I react to somethings differently now, so I am going to try them again.

how pathogenic heterozygote is , is nt clear. i read that some might even have increased physiological capacity. mustnt be worse.
also i could imagine that such a change could only affect if other factors come on top.
it even says that if there is myopathy there is most of the time a second disease at play.

 

[Shanti1]

For those who are interested, here is a pretty good write up on the condition: https://www.omim.org/entry/615511

 

[Kristianshaw87]

To check your 23andme SNP results to see if you have the adenosine monophosphate deaminase deficiency type 1 (AMPD1) allele, note that the ID for this SNP is rs17602729, according to Wikipedia.

So on 23andme, you can find your allele for this rs17602729 SNP HERE.


According to SNPedia, in your 23andme results shown at the above link, the risk allele for AMPD1 is A / A if you are homozygous (+/+), or A / G if you are heterozygous (+/-).

Those who do not have the risk allele for AMPD1 will be G / G in their 23andme results.

These values quoted are for positive strand orientation.

23andme always report allele orientation on the positive DNA strand, whereas SNPedia may report on the positive or negative strand. In the SNPedia page linked to above, they state at the top of the page that they are reporting on the negative strand, but we want the positive strand orientation, so you have to look at the "orientation reversed" results on that SNPedia page, which are the A/A, A/G and G/G values mentioned.



Apparently myoadenylate deaminase deficiency (MADD) is the old name for this metabolic disorder; it is now called adenosine monophosphate deaminase deficiency type 1 (AMPD1).

My knowledge and understanding of all things DNA related is pretty poor - what does it mean that mine is A/A for this SNP? Am I understanding that this is just a risk allele and not actually a diagnosis? Do I need to do anything about this? A lot of the symptoms from this particular deficiency sound just like ME/CFS and are things I experience

*edit - realised I accidentally clicked the next chromosome over on 23andme which was A/A - rs17602729 was G/G

 

[Hip]

what does it mean that mine is A/A for this SNP? Am I understanding that this is just a risk allele and not actually a diagnosis?

Your screenshot indicates you are G/G, not A/A. So you do not have the risk allele for AMPD1.

I have not read about adenosine monophosphate deaminase deficiency type 1, but I asked Perplexity how it is diagnosed, and this was the answer:

Adenosine monophosphate deaminase deficiency type 1 is typically diagnosed through the following methods 1 2 3 4 5:

1. Muscle biopsy: A muscle biopsy can be used to assess the activity of the AMP deaminase enzyme in the skeletal muscle. Histochemical staining or biochemical analysis of the muscle sample can show a lack of AMP deaminase activity, which is diagnostic for the condition.
2. Genetic testing: Genetic testing can identify the specific mutations in the AMPD1 gene that cause the deficiency. The most common mutation is the C34T substitution, which results in an early stop codon and prevents the synthesis of an active AMP deaminase enzyme.
3. Blood tests: Elevated levels of adenosine in the blood after exercise can also indicate AMPD1 deficiency, as the lack of AMP deaminase leads to the buildup of AMP and its metabolites.
4. Clinical presentation: The characteristic symptoms of exercise intolerance, muscle pain, cramps, and fatigue can also help guide the diagnosis, especially in individuals with a known family history of the condition.

In summary, the diagnosis of adenosine monophosphate deaminase deficiency type 1 is typically made through a combination of muscle biopsy, genetic testing, and clinical presentation. The muscle biopsy and genetic testing provide the definitive diagnosis, while the clinical symptoms help support the diagnosis.