Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)

[Valentijn]

Checked the forums. Most are completely empty or close to it.

The only one with any significant activity is http://www.experienceproject.com/groups/Have-Melas-Syndrome/98678 . It's had 50 "threads" posted in the past 7 years, some of which have responses.

One reports difficulty in managing diabetic ketoacidosis, and exercise intolerance:

I try to walk too, it's hard to walk a few blocks w/o muscle pain, and breathing issues, so they gave me 2 inhalers to help with opening up my airway b/c my chest would hurt and burn badly.

Another reports going into a less physically demanding job and says:

When I overdo it the first sign is digestive issues. This is my warning sign. I take good care of myself by listening to my body. When I feel tired I lie down. When I feel shaky, I eat. Some of my friends know about it but don't really understand.

Luckily I was a high-calibre athlete which I think helped with my endurance today, but I NEVER challenge myself now. For me it is more important for my brain to have it's energy needs met rather than impressing anyone else.

Sounds similar to PEM:

good days are still there but energy after a bussy couple days need 3 days of rest. tried to return to my old life as a logger and fireman but just am not able to

A man talking about his wife:

Back home but her quality of life seriousy affected by condition. She had to give up working in 2103 too fatigue and cant do much physical or strenuous tasks around house.

A 20 year old man:

However, All through my youth I always sat down because I was so tired ALL the time. Everyday since I can remember, an hour into the day feels like I ran a marathon and haven't sat down in days. I also have an incrediblly troubled time remembering things, long term and short term. Its very difficult to work, were as I am a line cook, but when Ithink about ssitting behind a desk and having responsibility with important documents or anything of that nature that would help my fatigue, I realise I can't trust my memory very much.

A woman regarding her son:

My 27 year old son "Skip" first presented with MELAS this May. He was in law school at the time and suddenly had a terrible headache and trouble reading and writing. An MRI confirmed a stroke to the left temporal lobe. We were so lucky an emergency room doctor suspected MELAS right then, and called for the genetic test. Skip suffered from muscle aches due to lactic acidosis as well. He dropped out of school and moved home with mom and dad to recover.

... In August Skip became very ill and was in the hospital 10 days with a bleeding ulcer. At the time he was diagnosed with diabetes as well. He is now on a low dose of insulin. Since then he has become much better, and it would be hard to tell that he has this debilitating illness. Still, life is slow on our farm, and Skip limits his activities

A mother:

This is my story on MELAS. It has given my loss of hearing, diabetes, TIA, muscle pain, migraines, acid reflux and more.

A sister:

My sister wasn't diagnosed with MELAS until the age of 13, she showed symptoms all her life. But no one had answers muscle cramps, asthma like breathing when she got around 19 or 20 that's when everything went downhill.

A familiar situation from someone diagnosed in the UK:

Everytime I go to the doctors or to see my consultant they make me feel as though thier's nothing wrong with me. But why am I in alot of pain in my back and legs and feet, I've just had to have an injection in my right shoulder because I couldn't lift my arm and I still can't hold anything heavy I think I'm gradually getting worse and yet the goverment as taken my ESA away from me recently and say I'm fit for work. I've appealed against it and I'm waiting to hear about it soon as it's gone to tribunal but I don't hold out much hope.

Mother misdiagnosed with ME, before MELAS discovered:

I am 33 years old and was diagnosed 3 years ago with MELAS as my mother who they suspected of having M.E for the previous 12 years turned out to not have that at all but have MELAS and she has over the years suffered every symptom in the worst case.

26 year old man:

I started having myoclonic seizures around 18, then falling when standing almost everytime for about a year, that went away but i developed extreme fatiuge and adhd. Physicaly i was weak, was never hungry, but nothing to make me concerned i had something serious

It sounds like damage is primarily the result of more severe strokes, versus stroke-like episodes or rare seizures.

 

[Jenny TipsforME]

It would be hard as a doctor to tell some of those accounts from ME I would think, and ME is much more likely incidence wise.

Do you think some of the early ME deaths could be missed MELAS?

ME would technically be a misdiagnosis, if there are exclusionary criteria in the definition used.

My question would then be do you have ME features which these people and the definition don't mention? Eg there doesn't really seem to be immune stuff here. Do you get the sore throat, fluey feeling type symptoms? Is sensory overload a thing in MELAS?

Nope And 23andMe doesn't test for the SNP which causes 80% of MELAS cases.

Huh all that data and the answers you need aren't often there. I didn't really need to know my eye colour, I can see that in the mirror!

If you want to pursue this will you get the relevant SNP tested?

 

[Sidereal]

I wonder if they prescribe GET for MELAS in the UK.

 

[Valentijn]

Eg there doesn't really seem to be immune stuff here.

Good point. I do have painful lymph nodes during a crash. No idea if that fits. But they can have symptoms aggravated or triggered by infections or (I think) immunizations.

Is sensory overload a thing in MELAS?

It probably comes with the brain inflammation. But again, haven't seen it mentioned.

If you want to pursue this will you get the relevant SNP tested?

I already know that I have a SNP on a MELAS-causing gene which has been flagged as pathogenic. So diagnostically, the next step would be a muscle biopsy. If it's MELAS, I should have ragged red fibers or certain other abnormalities.

 

[Valentijn]

I wonder if they prescribe GET for MELAS in the UK.

They'd probably try to

But producing lactate from exertion would often be a problem, so they shouldn't.

 

[Never Give Up]

Checked the forums. Most are completely empty or close to it.

The only one with any significant activity is http://www.experienceproject.com/groups/Have-Melas-Syndrome/98678 . It's had 50 "threads" posted in the past 7 years, some of which have responses.

One reports difficulty in managing diabetic ketoacidosis, and exercise intolerance:


Another reports going into a less physically demanding job and says:


Sounds similar to PEM:


A man talking about his wife:


A 20 year old man:


A woman regarding her son:


A mother:


A sister:


A familiar situation from someone diagnosed in the UK:


Mother misdiagnosed with ME, before MELAS discovered:


26 year old man:


It sounds like damage is primarily the result of more severe strokes, versus stroke-like episodes or rare seizures.

Holy s**t!

What is your plan for getting a diagnosis and treatment?

 

[Valentijn]

What is your plan for getting a diagnosis and treatment?

Tell the doc about my symptoms, how they're very similar to the lactic acidosis symptoms I got from the diabetes drug, and my pathogenic mutation. Ask for a referral to someone who specializes in mitochondrial diseases. Get a muscle biopsy.

 

[Valentijn]

My question would then be do you have ME features which these people and the definition don't mention? Eg there doesn't really seem to be immune stuff here. Do you get the sore throat, fluey feeling type symptoms? Is sensory overload a thing in MELAS?

Immune and sensory sensitivity aren't mentioned much in lists of symptoms and such, but there are case reports indicating that both are a problem. Hypersensitivity can occur during stroke-like episodes (similar to what you get from a migraine, I expect). Difficulties with recurring infections and associated symptoms might be due to difficulty in producing the energy needed to mount and sustain an immune response.

 

[Jenny TipsforME]

That would be actual recurring infections. I do get that unfortunately. But with ME I also get random viral symptoms which aren't in the order of a new viral infection. Sometimes it is hard to tell apart but I usually can.

Do you get this?

 

[Valentijn]

That would be actual recurring infections. I do get that unfortunately. But with ME I also get random viral symptoms which aren't in the order of a new viral infection. Sometimes it is hard to tell apart but I usually can.

Do you get this?

I have a Lyme & Bartonella infection from 20+ years ago that never really went away, apparently I test negative for ever having had EBV, which I think is the big one for recurring.

 

[Valentijn]

Research on glutamate dysfunction in MELAS: https://www.ncbi.nlm.nih.gov/pubmed/18455161

Basically there's a failure to transport it appropriately in neurons, which may result in excitotoxicity. This research involves a different SNP on a different gene (the most common one), but that's true of nearly all MELAS research.

These data suggest that a defect of glutamate transport in MELAS neurons may be due to decreased energy production and might be involved in mediating the pathogenic effects of the A3243G mtDNA mutation.

Could explain why my stroke-like episodes seemed to be triggered by MSG/E621, which is a form of unbound glutamate.

 

[Jenny TipsforME]

Do you react to these @Valentijn

MSG is out; glutamate is in
The food industry recognized that people were no longer going to purchase foods, or at least not in as great a quantity, that contains MSG. Instead, they started to take bound glutamate in food and unbound it by certain processes such as hydrolization, autolysis, modification and fermentation. Today, free glutamate is made not from MSG but instead comes from corn, molasses and wheat that has been processed to free the glutamate. Foods that contain this glutamate can be labeled MSG-free, even though they still contain glutamate.

Watch for these names on food labels:

• Hydrolyzed vegetable protein
• Hydrolyzed protein
• Hydrolyzed soy protein
• Soy protein concentrate (extract)
• Soy protein isolate
• Soy sauce
• Textured protein
• Whey protein concentrate
• Plant protein extract
• Sodium caseinate
• Yeast extract
• Autolyzed yeast

 

[Valentijn]

A case study initially posted by @Dolphin in another thread. The patient was initially misdiagnosed with Fibromyalgia, but featured exercise intolerance, so it was probably just an extra bad case of misdiagnosis

It includes a patient perspective, which is surprisingly helpful:

I am a 44-year-old woman with mitochondrial myopathy confirmed by blood tests and muscle biopsy. This disease grew worse as I aged and was exacerbated by pregnancy and other stressors. Certain medications really made me feel ill (which I now know to be mitochondrial killers). My main symptoms included muscle and joint pain, weakness, fatigue, muscle twitching, pain, headaches, and visual disturbances....

My feet, hands and legs were weak to where I fell several times down stairs and in my home. I was too weak to hold dishes and to wash them. Simple daily chores proved difficult, and at times I could not get out of bed or a chair without help. The fibromyalgia medicines did not help. As my symptoms waxed and waned, time and rest helped a bit.

Treatment with supplements was effective:

Subsequently, our patient was started on a regimen of coenzyme Q10 (Co-Q10; ubiquinone), creatine, carnitine, folic acid and a-lipoic acid. Co-Q10 transports electrons between complex I and complex III of the mitochondrial respiratory chain and has been shown to improve mitochondrial function in several studies [13]. Creatine generates additional ATP through the creatine phosphate shuttle. Carnitine enhances transport of fatty acids into the mitochondria. Folic acid is a cofactor for several mitochondrial enzymes, while a-lipoic acid is a strong antioxidant [14]. Although this treatment regimen was started several years after symptom onset, within the first few months our patient showed tremendous improvement. With continued therapy, her complaints dissipated over several months, with a gradual but sustained resolution of all symptoms.

They didn't find a known pathogenic mutation, but had several suspects, including a rare one on the same gene that mine is on (MT-DN1). Mitochondrial disease was confirmed with muscle biopsy, thought not by examining fibers.

 

[Valentijn]

I just got off the phone with my GP, regarding stopping the Metformin because it was causing me symptoms of lactic acidosis. She was surprised I stopped taking it, so I pointed out that the manufacturer advises stopping the drug and calling the doctor when developing those symptoms.

This didn't phase her, of course. First she wanted me to go back on the lower dose, even though I had already described being very sick and incapacitated from the higher dose for several days. She suggested the reaction wasn't due to the Metformin. I responded that the timing of the symptoms starting and stopping was unlikely to be coincidence, since the symptoms fit the lactic acidosis side-effects warning.

She wanted to know how my blood sugar was doing, and how often I was measuring. I told her I measure before meals and bedtime, and she wants me to measure less often - not on a daily basis. I told her I was going over 13.0 (235) frequently at bed time, and staying high through the night. She assured me that having it at 13 and higher for several more weeks is not a problem, and I shouldn't be in a hurry to get it down. I explained that I have a headache and nausea when it's that high, and don't want to eat anything then, so I definitely want it lower.

She's wary of increasing Gliclazide, because it can induce hypoglycemia by increasing insulin production. But she's doubling my dose from 30mg to 60mg, still all taken in the morning.

It's rather amusing to increase the risk of hypoglycemia while advising less blood glucose testing. Needless to say, I'll be ignoring the instruction to test less. And I'm happy to try increasing the Gliclazide. If my diabetes is the result of MELAS, the problem is with producing enough insulin, and not an inability of the pancreas to produce insulin.

 

[Valentijn]

Do you react to these @Valentijn

Yes, though they don't seem as bad. Basically I need to eat more of it or for a longer time to get a reaction. But I still avoid them completely, to the best of my knowledge

 

[Jenny TipsforME]

she wants me to measure less often

Concern about health anxiety? It is odd combined with her concern about hypoglycaemia. It also doesn't seem like hypoglycaemia is the immediate concern!

 

[Gingergrrl]

Val, can you switch GP's or is this not an option? Sorry if you already explained this!

 

[Valentijn]

Val, can you switch GP's or is this not an option? Sorry if you already explained this!

There aren't many options in our village, so I'm reluctant to do it. And this one's office is about two blocks away from our house.

 

[AndyPandy]

Just catching up on your posts @Valentijn. Sorry you are struggling with this.

I stopped Metformin in late October. I've had a noticeable increase in energy and can do quite a bit more but not a miracle cure. I have also been able to put on weight and don't need to eat every 2 hours to maintain weight. I'm a skinny Type 2. Gut issues have also improved but again no miracle.

I asked my specialist if I could come off it after doing some research into its adverse effects on ATP energy production and mitochondria. My BGLs are up but I'm going to explore an even lower carb diet to see if that helps.

I started getting muscle fatigue when I first started taking Metformin years ago but was told by various doctors that it could not be the cause. My ME really kicked off a few months later when I added statins into the mix.

Regarding testing I choose to test often so I know what is going on. Unfortunately the Australian Government has removed the subsidy for testing strips for people like me (Type 2). My GP says that testing strips don't improve management (which I think is ridiculous) so won't give me script for them at a reduced price. Just government penny pinching.

Regarding the drug you are taking (G .....) I found it did push me into hypos but I was also told that over time there is a risk that by pushing your pancreas to produce more insulin it will burn out your Beta cells. Not sure if I have that right and not able to confirm just now.

Anyway, I wish you all the best with this.

 

[AndyPandy]

BTW I've always been told to test before a meal and then two hours later. If I'm high before a meal I tend to have less carbs at that meal.