Is Oshtoran syndrome a real thing?

Hell if I know, even after a day of trying to find out.

I was prompted this morning to do a search for autoimmune conditions in VAERS this morning. It’s something I have been meaning to do. So, I did. And so begins another ‘fun’ deep dive.

If you search for a list of autoimmune diseases online, you’ll likely land on a Wikipedia page with a list of many known autoimmune diseases. One of the diseases in the list is called Oshtoran syndrome. I had never heard of it before today. Sounds like a species of alien from Doctor Who. It sits between Multiple Sclerosis and Progressive inflammatory neuropathy. Suitably so. I wondered why it was colored maroon and hovered my cursor over it to find that the ‘page does not exist’. Well, that’s odd, I thought. The immunologist in me took over, and I went on an online hunt for information on this syndrome. I found, very little. However, I did get a geography lesson on a beautiful corner of our globe that I knew literally nothing about.

https://en.wikipedia.org/wiki/List_of_autoimmune_diseases#cite_note-70

There is very little written online about this place and/or the meaning/association with the autoimmune disease. But, here’s what I learned. Oshtoran: It is pretty obscure and remote, and probably sensationally beautiful to see with one’s eyes, this Oshtoran village. They even have a castle!

https://www.itto.org/iran/photogallery/oshtoran-village-tuyserkan/

Etymology: Oshtoran or Ashtaran is a village in the province of Hamadan, Iran with a population of 1,328 people (365 families - 1 per day?) as of a 2006 census. It is a fantastically beautiful-looking place as you can see in the above photo.

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

But what about the syndrome? I found a reference that claimed this: Oshtoran syndrome is thought to have been so-named after Oshtorankuh in the Lurestan province of Iran. It is claimed that the first known patient had their origin there. Oshtorankuh is in the Zagros moutain range as seen in the stunning photo below. What’s strange about this is that Oshtoran (aka: Ashtaran) is not in Lorenstan province; it’s in Hamadan. It is unclear to me whether the syndrome is named after the town Oshtoran or the mountain range Oshtoran at this point, but the fact that it is unclear is weird to me. I have no idea of the true origins of this syndrome.

https://www.summitpost.org/oshtoran-kooh/304092.

Oshtorankuh means “mountain of camels” in Persian and is made of two words, “oshtoran” which is the plural form of ”oshtor” or “shotor” meaning “camel” with the plural suffix “an” and “kuh” that means “mountain”. So because of its eight high peaks of more than 4000 metres that look like a caravan of camels, this mountain is called “Oshtorkuh” or “Oshtorankuh”.¹

I should have been a linguist. So does this syndrome come from a camel? Or a people living in the mountains? Or from patient 0 living in the village of Oshtoran? Who knows.

Even though I still don’t know its exact origin story, I think we can concede that the disease called “Oshtoran syndrome” has its roots in rural Iran.

Also oddly, to me anyway, I found one link to a research group in Tel Aviv, Israel, that does research on this rare, heritable syndrome. There are 15 publications listed there, one of which is a case study on Oshtoran syndrome, another is about multiple sclerosis, another about nicotinic effects on cognitive function and another is about Lyme disease. Also weird, they were all published 6 years ago. That seems unlikely. Unless I am misinterpreting the word ‘publish’ here. I smell something fishy. A Pubmed search for papers on this syndrome returns nothing. I checked for published articles using keywords Oshtoran, Ashtaran and Oshtorankuh.

Let’s find out what this syndrome is and what it does, shall we? If we can. Alchetron has some information that you can also find here with ‘references’. These references look pretty bogus to me. I would really like to get my hands on the case study blurred out here. Et tu lorem ipsum?

Oshtoran Syndrome is a rare heritable neurological disorder with other organ systems involved as well, especially the liver, and the sympathetic nerve system. Patients suffering of Oshtoran Syndrome present symptoms affecting their cognitive functioning, psychiatric health, movement control, liver (fatty infiltration, hyperplastic nodules), fat metabolism, abnormal adrenal gland functioning and other issues which are caused by disturbed signalling functions in the nervous and other systems due to functional changes in a part of the immune system connected to a kynurenine pathway dysfunction.²

It is pretty easy to confuse this syndrome with other conditions like SLE, liver diseases, schizophrenia, dementia and many more diseases related to autoimmune conditions that affect many organ and organ systems with the most prevalent being the brain. ‘Oshtoran syndrome is thought to be caused by hyperactivity of the type-1 immune system leading to alterations in several organ functions like the kynurenine and glutamate metabolism, T-cell activation, fat metabolism etc. Please refer to these slides for a more complete history.’³

I feel like I have opened a stinky can of stupid sand worms. The weirdness around the obscurity of this neurological condition which, literally, describes, an encyclopedia of clinical conditions, could very well not be this so-called rare, heritable syndrome only found in a remote family lineage in a village in Iran. A disease associated with alterations in glutamate metabolism would be really bad news and would be linked to Parkinson’s and other neuro-degenerative disorders. Your brain can’t work properly without glutamate: it lets your neurons communicate.⁴ Too much or too little: bad news. Balance is required.

In addition to being a neurotransmitter, glutamate is the most abundant non-essential (our bodies make enough of it on their own) amino acid (building block of protein) made and stored in muscle tissue. It’s an important thing in human biology.

On kynurenine:

The kynurenine pathway has received increasing attention as its connection to inflammation, the immune system, and neurological conditions became more apparent. It is the primary route for tryptophan catabolism in the liver and the starting point for the synthesis of nicotinamide adenine dinucleotide in mammals. Dysregulation or overactivation of this pathway can lead to immune system activation and accumulation of potentially neurotoxic compounds.⁵

I am not sure what to make of this ‘syndrome’, but it is safe to say this: I had a simple task this morning: create a group of autoimmune MEDDRA keywords for a search and subsequent analysis of VAERS. I used the Wikipedia list. I found one entry that had been removed. I thought it odd and had never heard of it, so I searched for information on it. It led me to a syndrome (which is just a vague description of a bunch of symptoms) that is a neuro-degenerative disorder that involves glutamine and kynurenine alteration.

Another weird factoid on this Oshtoran syndrome. It is this very condition that a character in the Spider Man comics is meant to have (as well as his mother - she died from it) and he ends up being put in suspended animation to await a cure for it.

Here’s a paper called “An evaluation of extracts of five traditional medicinal plants from Iran on the inhibition of mushroom tyrosinase activity and scavenging of free radicals” published on ResearchGate. They found the plants in Oshtoran.⁶ Tyrosinase activity is linked to melanin and hyperpigmentation.

Sorry. One more thing. Perhaps the weirdest thing. There is actually a linked archive conversation about how to ‘Wikipedia’ this Oshtoran syndrome and the exchange is bizarre. They conclude that the syndrome is likely a hoax, haha!, but that if it is a hoax, then ‘then they've gone to a bit of work’ to make it seem like a real thing. My only question is: WHYYYYYYYY?

Well, whatever the reason byes, thanks for the geography lesson and for giving me an excuse to look at maps all morning. I LOVE maps. I should have been a cartographer.

Oh by the way, some VAERS stuff.

And no, there are no ‘Oshtoran syndrome’ reports in VAERS. But there are 11,716 neurotransmitter-related AEs reported to VAERS.

1. https://en.wikipedia.org/wiki/Oshtorankuh

2. https://alchetron.com/Oshtoran-Syndrome

3. https://slides.com/oshtoran_syndrome/oshtoran-syndrome/fullscreen#/1

4. https://my.clevelandclinic.org/health/articles/22839-glutamate

5. Davis, Ian, and Aimin Liu. “What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics?.” Expert review of neurotherapeutics vol. 15,7 (2015): 719-21. doi:10.1586/14737175.2015.1049999.

6. If something ‘weird’ happens to me today, it’s because of this article, by the way.