Unexplained hyperammonemia with loss of peripheral vision, HELP

waif

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I am asking for help on behalf of my friend. We are at a loss as to how to proceed from here..

He has chronically sky high ammonia levels and he is bedridden. For several years he was on depakote which is known to cause hyperammonemia. But he completely stopped the drug in 2015. Recently he rested and his ammonia was ~110ish, definitely >100 and he never tests in range. He briefly tried lactulose back in 2015, I believe, and it actually gave him horrible diarrhea for days and ironically caused his ammonia to spike. He has loss of peripheral vision, severe erectile dysfunction and his prolactin levels are slightly evelated...a 20 or so. His liver panel is healthy.

What kind of testing and specialists would you all recommend? I don't think his ammonia levels were caused by depakote anymore? We were thinking he needs a pituitary MRI to look for a tumor...at Johns Hopkins but that wouldn't explain his ammonia either. Huge thanks in advance.

Also, has anyone here been diagnosed with hyperammonemia? completely out of range?
 
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jeff_w

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I had high ammonia levels when I had SIBO (small intestinal bacterial overgrowth). After treating the SIBO with Xifaxan, my ammonia levels became normal. I was bedridden at the time, with POTS and fatigue, but I didn't have the loss of peripheral vision or other issues that he's having.
 

waif

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I had high ammonia levels when I had SIBO (small intestinal bacterial overgrowth). After treating the SIBO with Xifaxan, my ammonia levels became normal. I was bedridden at the time, with POTS and fatigue, but I didn't have the loss of peripheral vision or other issues that he's having.

this fascinates me because I actually had some xifaxan in my drawer...I took it for the heck of it, but i wish i had just given it to my friend. i don't want to lump in hyperammonia with all of his sx...i'm positive he has multiple issues. BUT his ammonia levels have been high for possibly a decade...

how high were your labs before taking the xifaxan? and what types of specialists did you see? thanks!
 

waif

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even if we could get his ammonia down for a few weeks that would be *something*

i have some notes on hyperammonemia, i'll just paste them here.
 

nanonug

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even if we could get his ammonia down for a few weeks that would be *something*
There's medication for hyperammonaemia. Is he taking anything? Completely eliminating protein from his diet could be helpful too. He needs a competent doctor looking into this, given the number of potential causes behind the problem.
 

waif

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I forgot about Carintine! I think he took it briefly...perhaps I can persuade him to take it again and get actual labwork to see if its effective.

We both like low carb diets...eating low carb and eliminating protein is difficult because he's already so thin. So I guess he needs to eliminate protein completely and swap it out for a few carbs with high fat.

these are promising:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359173/
A fasting serum ammonia level was markedly elevated at 276 μg/dL (normal: 40–80)...
The patient was administered thiamine, lactulose, and neomycin. Because of a deteriorating mental status and a continued rise in the fasting serum ammonia (which peaked at 582 μg/dL)........(!!!!!!)

Total parenteral nutrition (TPN) utilizing a calorically dense formula containing an amino acid profile rich in branched-chain amino acids and low in aromatic and ammonogenic amino acid was initiated. The diagnosis of carnitine deficiency was entertained, and serum total carnitine 22 mM (normal 33.8–77.5), free carnitine 19 μmol/L (normal 25–55), and acylcarnitine ester 3.0 μmol/L (normal 3.8–19) levels were subsequently found to be low. Oral levocarnitine (330 mg three times daily) was initiated and ammonia levels progressively declined to normal.....

She continues to do well 11 months after hospital discharge.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536406/

Because of the patient’s high ammonia concentration (>94 µg/mL), LCAR was added at 1 g/day. The patient was then monitored 2 months later at the doctor’s request; the results are shown:


Without LCAR /////// With LCAR
Blood VPA (mg/L) 86.6 /////// 46.3
4-en VPA (mg/L) 3.6 /////// 0.7
4-en-VPA/VPA metabolic ratio 0.042 /////// 0.015
Ammonium (NH+4) (µg/dL) 295 /////// 75
LCAR (µmol/L) 20.9 /////// 29.3
ACYLCAR/LCAR ratio 0.45 /////// 0.23
Effect of LCAR supplementation at 1 g/day

LCAR, L-carnitine; VPA, valproic acid; ACYLCAR/LCAR, acylcarnitine/L-carnitine


something else I forgot to mention in my initial post, he takes 10 mg of valium a day because cessation causes seizures...of some kind. but valium isn't correlated to hyperammonemia that i can tell. and seizures themselves apparently are linked to hyperammonemia *confused*


https://www.ncbi.nlm.nih.gov/pubmed/27768938
We speculate that the independent factors identified in the present study may be compatible with the hypothesis that muscular convulsion and/or respiratory failure during and after seizure is the primary cause of hyperammonaemia, although it is difficult to demonstrate directly.
 
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LINE

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I had high ammonia levels when I had SIBO (small intestinal bacterial overgrowth). After treating the SIBO with Xifaxan, my ammonia levels became normal. I was bedridden at the time, with POTS and fatigue, but I didn't have the loss of peripheral vision or other issues that he's having.
That is interesting. The article (link) I posted mentioned the idea that pathogenic organisms could be a caustive factor.
 

LINE

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My suspicion would be a vitamin co-factor problem, particularly something in the B family.

The mineral manganese is necessary for conversion, The Linus Pauling Institute says this:

"Arginase, another manganese-containing enzyme, is required by the liver for the urea cycle, a process that detoxifies ammonia generated during amino acid metabolism."
 
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crypt0cu1t

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I had high ammonia levels when I had SIBO (small intestinal bacterial overgrowth). After treating the SIBO with Xifaxan, my ammonia levels became normal. I was bedridden at the time, with POTS and fatigue, but I didn't have the loss of peripheral vision or other issues that he's having.
Did you notice a difference when the ammonia levels lowered?
 
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Hi @waif

Do you have any updates on your friend with hyperammonemia? I have a similar story and for four years doctors were blaming my symptoms on chronic fatigue. I never stopped looking for an answer and a year ago a geneticist discovered that I suffer from hyperammonemia, with my highest documented level being 105 umol/L (normal range is 12-47 umol).

In May 2018, my ammonia was at the 105 umol level and I was suffering from neurological related issues and having significant issues breathing. Doctors in Canada were working at a snails pace so I applied to go to the Mayo Clinic in Rochester and was accepted one week later. During my week at Mayo, doctors worked to rule out all the obvious causes (ie. liver, cancer, portal shunt, etc). Unfortunately, they were unable to come up with a diagnosis but indicated that my EMG was consistent with myasthenia gravis (MG) and recommended that I see a neurologist for follow-up and a metabolic specialist to rule out genetic causes of hyperammonemia.

I am now being seen by genetics, metabolics and internal medicine specialists back in Canada. My neurologist is useless and isn’t convinced that I have MG despite starting me on Mestinon for MG. I still don’t have a diagnosis but testing is ongoing. It’s important that your friend be seen by a metabolic specialist to rule out Urea Cycle Disorders (UCD) and other causes of hyperammonemia. OTC Deficiency is a UCD that can cause hyperammonemia and it can be extremely tricky to diagnose. A good metabolic specialist will be aware of the latest testing methods and therefore I suggest your friend seek a referral as soon as possible.

As an aside, I was taking lactulose for seven months and Rifaximin (antibiotic) for three months. Sometimes I wonder if the lactulose caused my ammonia levels to become inflated. Let me explain, lactulose causes diarrhea, diarrhea causes low potassium, and low potassium causes ammonia to elevate. In any event, both treatments were of minimal help but I’m curious to know how long @jeff_w took the antibiotics and if it successfully resolved all symptoms or if he needs to repeat the meds on a regular basis. The Rifaximin was successful at temporarily reducing my ammonia but as soon as I stopped taking the prescription my levels increased.

I subsequently started a very low protein diet and this has provided the best success at consistently reducing my ammonia levels down to the normal range. Unfortunately, there are many triggers (ie. eating protein, fasting, illness, hot weather, menstrual cycle, etc.) and there are days when it’s hard to eat low-protein, so I’m still figuring out how to manage on a day-to-day basis. The good news is that there have been some good improvements since I first learned about this metabolic condition in early-2018, so I can’t complain. In a nutshell, I can function again, albeit for a limited amount of time each day, but this is a step in the right direction.

As for symptoms, there were many that compounded and escalated over that four year period. The notables are: fatigue, ataxia, diplopia (I’ve since been diagnosed with convergence insufficiency aka exotropia), terrible pain on the side of my neck, rashes, pressure and pain in my head (which has since been explained as likely being caused by encephalopathy as a result of the hyperammonemia), etc.

I can’t tell you how many times I had trouble walking, talking and functioning in front of my family doctor and at the ERD, and not once did someone test my ammonia, NOT ONCE!! Instead they blamed it on Chronic Fatigue, depression and anxiety - all of which have since been ruled out by the appropriate professionals. Sadly, it took four years and a geneticist to have this routine test completed.

In the event that someone is reading this post and going through a similar experience, allow me this opportunity to state the obvious...THERE IS NO ANTIDEPRESSANT OR PAIN PILL THAT WILL HELP SOMEONE WITH HYPERAMMONEMIA, in fact it could cause a metabolic crisis. Shame on these pill pushers, I mean doctors, that prescribe these drugs to people that aren’t depressed or in pain. People, please spread the word and have your ammonia tested (both fasting and postprandial) if doctors are telling you it’s Chronic Fatigue. In my opinion, they use this label to get you to stop asking questions.

In any event, I hope your friend is getting some answers from the right specialists. Please send an update on any progress/setbacks he’s had since your initial post and I’ll send updates from my end, if anyone is interested. Take care
 
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I forgot about Carintine! I think he took it briefly...perhaps I can persuade him to take it again and get actual labwork to see if its effective.

We both like low carb diets...eating low carb and eliminating protein is difficult because he's already so thin. So I guess he needs to eliminate protein completely and swap it out for a few carbs with high fat.

these are promising:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359173/
A fasting serum ammonia level was markedly elevated at 276 μg/dL (normal: 40–80)...
The patient was administered thiamine, lactulose, and neomycin. Because of a deteriorating mental status and a continued rise in the fasting serum ammonia (which peaked at 582 μg/dL)........(!!!!!!)

Total parenteral nutrition (TPN) utilizing a calorically dense formula containing an amino acid profile rich in branched-chain amino acids and low in aromatic and ammonogenic amino acid was initiated. The diagnosis of carnitine deficiency was entertained, and serum total carnitine 22 mM (normal 33.8–77.5), free carnitine 19 μmol/L (normal 25–55), and acylcarnitine ester 3.0 μmol/L (normal 3.8–19) levels were subsequently found to be low. Oral levocarnitine (330 mg three times daily) was initiated and ammonia levels progressively declined to normal.....

She continues to do well 11 months after hospital discharge.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536406/

Because of the patient’s high ammonia concentration (>94 µg/mL), LCAR was added at 1 g/day. The patient was then monitored 2 months later at the doctor’s request; the results are shown:


Without LCAR /////// With LCAR
Blood VPA (mg/L) 86.6 /////// 46.3
4-en VPA (mg/L) 3.6 /////// 0.7
4-en-VPA/VPA metabolic ratio 0.042 /////// 0.015
Ammonium (NH+4) (µg/dL) 295 /////// 75
LCAR (µmol/L) 20.9 /////// 29.3
ACYLCAR/LCAR ratio 0.45 /////// 0.23
Effect of LCAR supplementation at 1 g/day

LCAR, L-carnitine; VPA, valproic acid; ACYLCAR/LCAR, acylcarnitine/L-carnitine


something else I forgot to mention in my initial post, he takes 10 mg of valium a day because cessation causes seizures...of some kind. but valium isn't correlated to hyperammonemia that i can tell. and seizures themselves apparently are linked to hyperammonemia *confused*


https://www.ncbi.nlm.nih.gov/pubmed/27768938
We speculate that the independent factors identified in the present study may be compatible with the hypothesis that muscular convulsion and/or respiratory failure during and after seizure is the primary cause of hyperammonaemia, although it is difficult to demonstrate directly.
Do you think its necessary to eliminate proteins entirely? What about 3grams of fish per day? My ammonia is very high...
 

waif

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Hi @LegallyRed

I hope you're still browsing these forums, I know it's been a while. I'd love to hear updates.

my friend's condition has deteriorated to the point where he can't get up and go to the bathroom or to get food. And I don't live near him to help. We're actually fearful to go to the doctor because of covid to get his ammonia levels checked and the blood test at his condo would be inaccurate. I emailed the director of UCD disorders for advice (precovid) and she made it a big deal about the blood test being STAT and immediately put on ice.

He also has kidney stones. I wonder if these are somehow related.
 

S-VV

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Listen, hyperammonemia can cause irreversible excitotoxic neurological damage very fast. Sodium Benzoate and phenylbutyrate are clinically available ammonia “chelators” that any doctor can prescribe. Citruline has been shown to be helpful, alpha keto-acids as well. Rifaximin can help if the burden comes from the microbiome. A low carb diet will increase ammonia due to the increased gluconeogenesis from amino acids.

I would find a telemedicine doctor ASAP and treat empirically. Your friend cant afford to wait for a drawn out diagnostic process.
 

waif

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Listen, hyperammonemia can cause irreversible excitotoxic neurological damage very fast. Sodium Benzoate and phenylbutyrate are clinically available ammonia “chelators” that any doctor can prescribe. Citruline has been shown to be helpful, alpha keto-acids as well. Rifaximin can help if the burden comes from the microbiome. A low carb diet will increase ammonia due to the increased gluconeogenesis from amino acids.

I would find a telemedicine doctor ASAP and treat empirically. Your friend cant afford to wait for a drawn out diagnostic process.
I forwarded this information to him that's *very* useful, do you know how to find a good telemedicine doctor? I'm worried that they will want to see him for the initial visit in the office

Money is not an issue. He'd pay a lot for a good telemedicine doctor.