The Genetic Cause of my Chronic Illness

ChristianBonanno

Active Member
I did not know where else to put this, because it is not really (yet) a recovery story, but kind of is since I am med free but fro an occasional Klonopin but I still have extreme sensitivities. Many of you would have known me here as "Croatoan" back in 2016 when I vanished to just focus on my research. Well that research has paid off and now I know the cause and the process for my complex chronic illness.

First, a list of my reoccurring maladies.
  • Bipolar Disorder Schizoaffective Type
  • OCD
  • Panic Disorder
  • Aspergers
  • Insomnia, Nightmares
  • Labile Hypertension
  • Dyslexia
  • Interstitial Cystitis
  • Chronic Fatigue
  • Fibromyalgia
  • Costochondritis
  • Plantar Fasciitis
  • Dupuytren's Contracture
  • Cryptorchidism
  • Duodenitis
  • IBS-D
  • Uveitis
  • Reoccurring Monocytosis and low WBC
  • Seborrheic Dermatitis
  • Hyperlipidemia
  • Lung Nodules (Noncancerous)
What I have discovered is that I have Partial Purine Nucleoside Phosphorylase Deficiency.

Purine Nucleoside Phosphorylase plays a role in the purine pathway that eventually ends up to make uric acid and is pretty much at the beginning of the pathway and it is responsible for converting Adenosine, Inosine, Xanthosine, and Guanosine.

PNP.jpg


The slowdown of this enzyme leads to a buildup of ATP, GTP, and dGTP which causes everything from immune deficiency to neurological disorders.

In a complete deficiency, symptoms are seen at a young age, but with a partial deficiency the worst symptoms usually appear when the person in the 30's. And well, that is when I became sick and have since been living on Disability 25 years ago.

So why was this causing all my symptoms.

The first was the immune deficiency. The changes in this gen that I have cause what is known as an S Phase block in T cells, rendering them mostly useless and triggering the symptoms of Lupus. They kept thinking I had Lupus but I never had the antibodies, and the reason is that this is a unique form of lupus. I get the Mahlar Rashes and even Shuster's Sign, but this always had them scratching their heads. But anyway, basically it made me susceptible to infection but not bad enough that I would die ro my WBC would drop to a point to make someone care. Here is a graph of some of my WBC results. I feel that zinc help bring up my WBC. I also believe this is what is responsible for my Lung Nodules.But you can see in the graph when I was taking a lot of zinc. Also, my constant monocytosis is certainly linked to PNP Deficiency.

wbc.png


mono.png


So I think this was what was casuing the "ME/CFS" part of my illness, mainly the PEA, and brain fog stuff.

But what else is happening is way more interesting.

The build up of ATP and GTP also sensitizes what are called the G Protein-Coupled Receptors. So the more GTP in the cell, the more sensitive you will be to say Norepinepherine and the more ATP, the more cAMP you will make to trigger a whole chain of reactions. Here is good video showing how GTP activates these receptors and how ATP increases cAMP:


So by having this partial PNP deficiency I get a build up of ATP and GTP and, as a result, hundreds of the g protien-coupled receptors or amped up and ready to act whenever they are even slightly triggered. To get a look at all of the receptors, see this list.


And this explains all the sensitivities I have, from how smoking pot cripples me with anxiety (Cannabinoid receptors), my other mood disorders (Serotonin and Dopamine Receptors), my hypercalcemia when taking small doses of Vitamin D (Parathyroid hormone receptors), my Intersital Cystitis (the Transient receptor potential channel), and even my Asperger's (Oxytocin Receptors). That last receptor is probably the most interesting since one of them, TRPV1, it is on the skin as well as in the body and is the receptor for hot pepers (capsacin) and heta and can even be triggered by Electromagnetic Radiation.

And this is what triggers my "Mania", my "upness" and my seemingly unending energy, a shit ton of ATP.

Here are the list of my PNP SNPs I pulled from 23andMe, my SNPs are in the first row and I have the genetics of a bunch of others after as a comparison.

SNPs.png


The most relevant of these SNPs is rs1049564 which is featured in this study:
Lupus-Associated Functional Polymorphism in PNP Causes Cell Cycle Abnormalities and Interferon Pathway Activation in Human Immune Cells

rs1049562, rs1049564 and rs1713421are in what is called Linakage Disequlibrium, meaning if there is a change in one the rest will carry the same minor or major allele.

But my rs1049562 polymorphisms confer a functional change, which means it slows down the enzyme.

So, what do I do about this? I think zinc plays a role in increasing phosphate availability for PNP. and I have some severe polymorphosms in PDE4B which caused my Cryptorchidism and PDE4B uses zinc as a cofactor and also helps me get rid of my high cAMP.
PDE4-inhibitors-in-the-regulation-of-inflammatory-responses-36-38.png


But I think the biggest help will be lowering calorie intake dramatically. I always felt better when I fasted and when I ate less, and eating less will lower ATP and GTP for sure because that is where we get all our ATP and GTP.

Also, finding out I had Sami heritage helped me understand that these sensitivities served a purpose living in a cold climate, and eating like a Sami has helps me a lot. Very few carbs and veggies, some berries and a lot of high omega 3 food like shellfish, salmon, venison, etc..

So, how can this help all of you struggling with pretty much the opposite what I have? I believe most of you are suffering from low ATP and GTP. For example I have hypertension and most of you have POTS or hypotenstion. This is because your G Protein Coupled Receptors are lacking thet GTP and ATP to become sensitive enough even when you get norepinepherine.

And while zinc is important for me, I believe that Magnesium and/or Manganese will be just as important for some people who are the opposite of me since it is uses to make cAMP out of ATP via Adenylyl Cyclase. For others it may be an issue with insulin resistance or something in the glycolosis pathway. It will for certain be deterrent for everyone.

Anyway, that's all I go for now. Wishing you will and wish me luck.
 

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ChristianBonanno

Active Member
@ChristianBonanno
You’ve done incredible work to solve this puzzle, it’s impressive. Are you starting to feel better with your new way of eating plus zinc?

Thanks.

I am feeling more stable but I think understanding what is happening helps the most. It is still a tricky thing to handle because I am sensitive to so many things and there are so many things I still cannot eat and drink. And I am having a hard time with the calorie restriction.

Plus I started taking Vitamin D last month, not a lot at all and not for long, and I just found out my calcium is little high. It seems the Parathyroid hormone receptor is a GPCR so I was sensitive to that as well. So now I need to restrict some vitamin D foods for a while.

calcium.png


But the zinc helps, and it always helped me. I just finally discovered why.
 

Aidan Walsh

Well-Known Member
I
I did not know where else to put this, because it is not really (yet) a recovery story, but kind of is since I am med free but fro an occasional Klonopin but I still have extreme sensitivities. Many of you would have known me here as "Croatoan" back in 2016 when I vanished to just focus on my research. Well that research has paid off and now I know the cause and the process for my complex chronic illness.

First, a list of my reoccurring maladies.
  • Bipolar Disorder Schizoaffective Type
  • OCD
  • Panic Disorder
  • Aspergers
  • Insomnia, Nightmares
  • Labile Hypertension
  • Dyslexia
  • Interstitial Cystitis
  • Chronic Fatigue
  • Fibromyalgia
  • Costochondritis
  • Plantar Fasciitis
  • Dupuytren's Contracture
  • Cryptorchidism
  • Duodenitis
  • IBS-D
  • Uveitis
  • Reoccurring Monocytosis and low WBC
  • Seborrheic Dermatitis
  • Hyperlipidemia
  • Lung Nodules (Noncancerous)
What I have discovered is that I have Partial Purine Nucleoside Phosphorylase Deficiency.

Purine Nucleoside Phosphorylase plays a role in the purine pathway that eventually ends up to make uric acid and is pretty much at the beginning of the pathway and it is responsible for converting Adenosine, Inosine, Xanthosine, and Guanosine.

View attachment 3447

The slowdown of this enzyme leads to a buildup of ATP, GTP, and dGTP which causes everything from immune deficiency to neurological disorders.

In a complete deficiency, symptoms are seen at a young age, but with a partial deficiency the worst symptoms usually appear when the person in the 30's. And well, that is when I became sick and have since been living on Disability 25 years ago.

So why was this causing all my symptoms.

The first was the immune deficiency. The changes in this gen that I have cause what is known as an S Phase block in T cells, rendering them mostly useless and triggering the symptoms of Lupus. They kept thinking I had Lupus but I never had the antibodies, and the reason is that this is a unique form of lupus. I get the Mahlar Rashes and even Shuster's Sign, but this always had them scratching their heads. But anyway, basically it made me susceptible to infection but not bad enough that I would die ro my WBC would drop to a point to make someone care. Here is a graph of some of my WBC results. I feel that zinc help bring up my WBC. I also believe this is what is responsible for my Lung Nodules.But you can see in the graph when I was taking a lot of zinc. Also, my constant monocytosis is certainly linked to PNP Deficiency.

View attachment 3448

View attachment 3452

So I think this was what was casuing the "ME/CFS" part of my illness, mainly the PEA, and brain fog stuff.

But what else is happening is way more interesting.

The build up of ATP and GTP also sensitizes what are called the G Protein-Coupled Receptors. So the more GTP in the cell, the more sensitive you will be to say Norepinepherine and the more ATP, the more cAMP you will make to trigger a whole chain of reactions. Here is good video showing how GTP activates these receptors and how ATP increases cAMP:


So by having this partial PNP deficiency I get a build up of ATP and GTP and, as a result, hundreds of the g protien-coupled receptors or amped up and ready to act whenever they are even slightly triggered. To get a look at all of the receptors, see this list.


And this explains all the sensitivities I have, from how smoking pot cripples me with anxiety (Cannabinoid receptors), my other mood disorders (Serotonin and Dopamine Receptors), my hypercalcemia when taking small doses of Vitamin D (Parathyroid hormone receptors), my Intersital Cystitis (the Transient receptor potential channel), and even my Asperger's (Oxytocin Receptors). That last receptor is probably the most interesting since one of them, TRPV1, it is on the skin as well as in the body and is the receptor for hot pepers (capsacin) and heta and can even be triggered by Electromagnetic Radiation.

And this is what triggers my "Mania", my "upness" and my seemingly unending energy, a shit ton of ATP.

Here are the list of my PNP SNPs I pulled from 23andMe, my SNPs are in the first row and I have the genetics of a bunch of others after as a comparison.

View attachment 3450

The most relevant of these SNPs is rs1049564 which is featured in this study:
Lupus-Associated Functional Polymorphism in PNP Causes Cell Cycle Abnormalities and Interferon Pathway Activation in Human Immune Cells

rs1049562, rs1049564 and rs1713421are in what is called Linakage Disequlibrium, meaning if there is a change in one the rest will carry the same minor or major allele.

But my rs1049562 polymorphisms confer a functional change, which means it slows down the enzyme.

So, what do I do about this? I think zinc plays a role in increasing phosphate availability for PNP. and I have some severe polymorphosms in PDE4B which caused my Cryptorchidism and PDE4B uses zinc as a cofactor and also helps me get rid of my high cAMP.
View attachment 3451

But I think the biggest help will be lowering calorie intake dramatically. I always felt better when I fasted and when I ate less, and eating less will lower ATP and GTP for sure because that is where we get all our ATP and GTP.

Also, finding out I had Sami heritage helped me understand that these sensitivities served a purpose living in a cold climate, and eating like a Sami has helps me a lot. Very few carbs and veggies, some berries and a lot of high omega 3 food like shellfish, salmon, venison, etc..

So, how can this help all of you struggling with pretty much the opposite what I have? I believe most of you are suffering from low ATP and GTP. For example I have hypertension and most of you have POTS or hypotenstion. This is because your G Protein Coupled Receptors are lacking thet GTP and ATP to become sensitive enough even when you get norepinepherine.

And while zinc is important for me, I believe that Magnesium and/or Manganese will be just as important for some people who are the opposite of me since it is uses to make cAMP out of ATP via Adenylyl Cyclase. For others it may be an issue with insulin resistance or something in the glycolosis pathway. It will for certain be deterrent for everyone.

Anyway, that's all I go for now. Wishing you will and wish me luck.
Hi, glad you are doing better. Does this mean all the things above you mentioned are no longer diagnostic the numerous things you posted top?

I have the Raw Data from 23andme health ancestry I need someone to read it all do you have a link where I can get it read all DNA online?

Have you checked for ALDOB & ALPHA 1? I will look at my Raw Data to see if I have these Genes you mentioned. Wish you wellness soon
 

Aidan Walsh

Well-Known Member
Thanks.

I am feeling more stable but I think understanding what is happening helps the most. It is still a tricky thing to handle because I am sensitive to so many things and there are so many things I still cannot eat and drink. And I am having a hard time with the calorie restriction.

Plus I started taking Vitamin D last month, not a lot at all and not for long, and I just found out my calcium is little high. It seems the Parathyroid hormone receptor is a GPCR so I was sensitive to that as well. So now I need to restrict some vitamin D foods for a while.

View attachment 3454

But the zinc helps, and it always helped me. I just finally discovered why.
What brand & dose of Zinc are you taking now?
 

Aidan Walsh

Well-Known Member
Check also MTHFR & COMT, folic acid not to be taken even in Flour. methyl folate methyl B-12 or folinic acid ok. Avoid flour Foods unless flour is 100% Organic & run from additives in countless foods vitamins minerals
 

ChristianBonanno

Active Member
I

Hi, glad you are doing better. Does this mean all the things above you mentioned are no longer diagnostic the numerous things you posted top?

No, some are obviously irreversable, most have declined dramatically, some are gone completely. I am just in the beginning of my treatment really.

I have the Raw Data from 23andme health ancestry I need someone to read it all do you have a link where I can get it read all DNA online?

Upload you raw data to


It makes it easier to find less common SNPs and look at specific genes. You can also download the results.
 

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