Nobody Has My Condition but Me

I can second this recommendation. Matt’s team at UAB helped collect and analyze the latest research and suggest clinical treatments for my son’s rare genetic variant. It’s free and they were great to work with.

There also is the Undiagnosed Disease Network which is NIH funded.

https://undiagnosed.hms.harvard.edu/about-us/

I heard a talk from Hugo Bellen which was interesting about this research. And using model organisms to in a sense verify that they're going in the right direction. https://flypush.research.bcm.edu/lab/about-mosc-udn.htm I haven't had personal experience, but what I remember from the talk it was clear some mutations where causing over expression which was hard to figure out in the patient.

Is this for people who have symptoms but have not received a clear diagnosis from anyone? Or for people who already have a clear diagnosis of a rare condition?

> and former Obama-admin CTO for the US.

Is this part supposed to make me trust him?

For those interested in Matt Might's work I'd recommend this talk he gave at Jane Street: https://www.youtube.com/watch?v=Rt3XyeFHvt4

How do you know you have an autoimmune disease? Did those doctors diagnose you with one and then proceed not to take you seriously?

I'm in the same boat - unknown autoimmune disease, talked to teams of neurologists in different health networks. All they can do is prescribe treatment for symptoms, not causes, which is frustrating.

How does one even go about sequencing their DNA?

not knowing is one thing, not taking things just a bit seriously is a breach of medical professionalism. it's very common sadly

> nobody has said, "We should consider looking at your DNA to see what's up here. I'm really interested and want to figure this out with you."

The vast majority of doctors don't have the expertise or resources needed to do that. A doctor can't write a script for whole genome sequencing just to see what turns up - it will be rejected by insurance 100% of the time because that's going outside the scope of standard practice. And even if they did manage to sequencing done and a novel mutation popped up, there isn't anything to do with that treatment-wise. The next step would be going back to the lab, synthesizing mutant RNA and/or peptide sequences and studying their properties. And it would likely take years for that to translate into knowledge that is clinically useful.

If you want that kind of care, you need a large, academic hospital that has an ultraspecialist with an active and well funded research program in the relevant area. They can cover the costs of nonstandard tests out of their research funds. And if unusual findings pop up, they have the equipment/resources to follow that up with further studies.

This could be true for many professions. If I need some long-tail obscure help (suppose, for example, my car was acting up in a strange way the mechanic never had seen or heard of before) I'd expect roughly the same set of reactions. Most professionals are state machines that do X Y Z well. You throw A B C at them and few will introspect deeply into it.

I do clinical genomics. Highly recommend you to find a university hospital that can do genomic analysis for you. The IUIS IEI list has ~500 known genes that could be causal if you have some variant in one of these genes. The key is a good bioinformatic interpretation and clinical follow up.

There are even some good commercial options that might be able to detect a causal variant. These guys can do it after order via healthcare professional https://blueprintgenetics.com/patients/?group=ordering-patie...

or these guys can do it from home; first the genome sequencing and then the immune panel report https://dantelabs.com/products/autoimmunity-panel

Likelihood of finding causal variants has doubled in last 5 years.

* IUIS page: https://iuis.org/committees/iei/

* latest version of gene list: https://static-content.springer.com/esm/art%3A10.1007%2Fs108...

* from this paper: https://link.springer.com/article/10.1007/s10875-022-01289-3

Great info also in IPOPI website https://ipopi.org/about-ipopi/mission-and-objectives/

> "I'm not sure what is going on here and I don't know how to help you,"

In my experience even this is significantly better than you'll get out of the average doctor. I'd gladly see a doctor who was willing to say "yeah, something is wrong but I have no idea what" instead of being dismissive.

> but nobody has said, "We should consider looking at your DNA to see what's up here. I'm really interested and want to figure this out with you."

You could sequence your own genome and use a service to compare it against the ClinVar database that correlates genetic variations with research.

Odds are that you won't find anything useful to your specific condition.

Most autoimmune issues are acquired, not genetic. With few exceptions, the common genetic variations associated with many diseases can't be used in a diagnostic manner. A genetic variant that increases your odds of contracting a rare disease by 10X might sound significant, but if it's truly a rare disease then you could be going from 0.001% to 0.01% odds.

The unfortunate truth is that if your condition doesn't match something that can be diagnosed with the tests available to your doctors, there isn't much they can do to forge ahead with new research on their own. That's the role of researchers, not doctors. And it takes decades to get to the bottom of conditions, if ever.

You might have some luck scouring the internet for similar-sounding conditions and groups who research them. Occasionally you can find your way into clinical trials or registered on waitlists for researchers who might need candidates to test.

While I (probably) don't have an autoimmune disease, in knowing that I'm not the only person that have experienced that sort of helplessness navigating my way through the medical system, without even finding a defining name for the condition in question. I tried searching online for the symptoms only to find very general cases that do not have some of the main characteristics. Quite the same feeling one gets when they search for an error message only to find the source code that raises that exception. :)

Sometimes I think the medical issue I'm suffering from is annoying enough but not being able to diagnose it just adds an insult to injury. Is it that I cannot express my problem well enough to find similar cases online? Is this such an obscure case or maybe a lot more people are experiencing it but they just handle it so much better that they don't feel the urge to complain about it?

Just to be more specific and less mysterious, I'm suffering from mild chronic joint pains, in pretty much every joint starting from ankle, knee, lower back, neck, elbow and hand. The tricky bit, and the reason I didn't use plural, is that the pains only occur on either left side or right side of my body, but only one side at a time, usually the pains will switch sides (left <=> right) overnight (though not every night). It has low correlation with the intensity and volume of physical activity I'm doing. Blood tests show nothing out of the ordinary, C.T shows that I do have mild case of bulging discs in my back, which would have explained back pains (which I have) but not the issue of feeling them in just one side (along with every other joint in that side). These pains, mild as they are do not respond in any way to NSAIDs. Popping my knuckles (and every other joint you can think of) helps momentarily. If the pain level is above normal, sleeping is affected too (in fact it's almost always affected to some degree), which in turn amplify the pains as poor sleep would do.

Nerve conduction tests also revealed nothing and the doctors I've seen couldn't offer any observation. The fact that I have quite an athletic build doesn't help either since doctors note that and assume that I'm doing just fine. In fact though, these pains, which have started in my teenage years and have become worse in my early twenties (I'm in my late thirties now) take a daily toll on me, in terms of sleep, fatigue and my attention span.

I'm lucky to have been very healthy in my life other than that, but I feel that I could have done so much better if I didn't have that invisible medical issue affecting me every day.

I had same thing. Mystery condition. Symptoms started in high school. Doctors always brushed off concerns. 20 years later, Finally body collapsed 2 years and dozens of doctors appointments to finally figure out its autoimmune Sjogrens. Second most common autoimmune after Lupus.

However doctors says I can’t have it since I’m male.

Took another year to get all the test runs and to start treatment. Doctors fighting at every step. Only when I had drastic improvement from treatment did they finally take me serious.

Apparently my situation is typical for Sjogrens.

> Some prescribe me something and say "see if that helps,"

That's pretty much all they're doing with her, too.

They don't seem to be close at all at actually solving her problem. I'd summarize her story as "thanks for your unique blood, it may help us create medical miracles one day. in the meantime, try this new drug, it might do something"

Most doctors, unfortunately, are pharmacological resellers. They get a list of medicines for symptoms and they prescribe it. A surprisingly high percentage of them will prescribe you these medicines regardless of your symptoms or condition.

Doctors who have a specialized and sophisticated area of expertise do exist, but they are 1. very expensive and 2. rare and between.

tl;dr: most doctors don’t give a flying f— about you or your condition.

There are companies out there who have extensive data on which of hundreds of genetic SNPs (single nucleotide polymorphisms) correlate to which conditions that have a genetic component. They take a DNA sample, run it through their assays, and then they give you a sixty (or whatever) page laymen's description of what all your various SNPs mean for you from a medical perspective. They then give your doctor a one hundred (or whatever) page detailed description which can then be used to guide your medical care in a wide variety of areas.

For example, there might be three different main SNPs that relate to vitamin B-12. One might relate to how easily your body absorbs it. One might relate to how fast your body consumes it. One might relate to how it is disposed of in your body. And if you have the bad version of each of these SNPs, then that has a huge impact on your life -- because vitamin B-12 turns out to be pretty important (see https://www.mayoclinic.org/drugs-supplements-vitamin-b12/art... ).

But, there might be things you can do to improve your situation related to vitamin B-12, such as always using the methylated version. And maybe you just need to consume a lot more vitamin B-12 than most people. These are things your doctor can help you with, once they are armed with the DNA data.

I'm not going to mention company names here, because we have a connection to the company we've used. And this is an expensive service. So, I don't want to be accused of shilling for this company.

But my wife has already had her test. And I'm planning on getting mine as soon as I can.

And there are multiple companies in this space. Even if you don't use the same company we have, I think the important thing is that if you have major medical problems that are unexplained or difficult to address, then I think this is the kind of service that you might want to look into.

It might have helped that she works at Yale, and that's where she initially went for care:

> "As a professor at Yale, I receive my medical care through the university's health center, a private bastion of socialized medicine [...]"

Not even complex medical conditions; a friend with stomach pain issues was being blown off by doctors with "just lose weight" for a year before she collapsed on the sidewalk. In the hospital, they removed a 30-lb cyst from her abdomen, but I'm not sure diet and exercise would have helped with that particular weight loss.

It sounds like the obviously swollen hand was a big symptom, at least for the doctor who immediately said, "That's not rheumatoid arthritis."

To use the zebra analogy, it sounded like that was the part where the doctor said, "I don't know wtf this is, but it's not a horse."

I have a friend, he gets wild migraines all the time. Dozens and dozens of doctors over 25 years. All he can say at this point is what he thinks doesnt cause them. The issue is diagnosing these sorts of things is tough. You can not exactly crack someone open and poke around and not possibly break things plus the cost of time and money. So you mostly look at the symptoms and hope you can read the tea leaves and get it. For most things that works pretty good. But get a bit out of field of what they do and you will have a bad time with most doctors unless they happen to read the tea leaves correctly. My mother in law went from 'you have the flu' to 'you have stage 4 single cell' in under a week and was dead soon after. She went to the doctor dozens of times about it the months before. We get this idea that doctors are miracle worker wizards. But sometimes you feel like they are playing with bear skins and arrow heads.

> despite also having observed cardiac symptoms that worsen to any exercise.

Isn't this the exact reason they should exercise? I'm sure the symptoms present worse during exercise, but the exercise itself will gradually make your body more resilient or even cure many cardiac issues. I'm unaware of any cardiac disease that gets worse with some form of exercise, granted there are levels of intensity in exercise no one should be attempting without proper conditioning.

> I have multiple friends who get told to just get more fit, despite also having observed cardiac symptoms that worsen to any exercise.

Clinically, it's rare for people (below retirement age) to have cardiac conditions that exclude any exercise.

I don't know your friends' details, but a common pattern in these situations is for there to be a misunderstanding about what "exercise" means. If someone is having life-threatening cardiac symptoms, no reasonable doctor is going to recommend that they just go to the gym and sweat it out. In the worst cases, what they're trying to avoid is the deconditioning slide that comes with chronic illness. The goal isn't to get fit or go for runs or push to exhaustion. The goal is to slow the physical health decline that comes with being too sedentary.

It can be counterintuitive, but doing extremely light activity (walking 0.1 miles per day, working up to 0.4 miles per day) can be extremely beneficial compared to avoiding activity altogether, even if it's uncomfortable.

Once the fitness is gone, it's hard to get it back. A lot of patients start out with one condition, which then becomes a combination of that condition plus a year of deconditioning.

Physical therapists trained in chronic illness specialize in these treatments and adapting to the bounds of any cardiac limits.

I was reading along and thinking to myself "gee, this sounds a lot like Lyme" and sure enough, she mentions she tested positive for it.

I imagine the NIH docs would have thought of that already though. I do wonder if there is an interaction between the wonky IgG/IgM and the spirochetes, that could be studied and lead to insights into Lyme.

She was a guest on Know Your Enemy recently, which is a nice intro to Hoover and the book.

I found my own genetic condition this way. hEDS/clEDS from a TNXB mutation. I already had a strong indication that I had this by noticing rare behavior about myself was similar to other people with TNXB mutations. DNA sequence confirmed it. The vast majority people with this condition will never get a positive diagnoses from a doctor no matter how many they see, but it’s clear as day right there in the DNA.

My wife has this, she's had half a dozen lung collapses over the last few years as the nodules separate lung from lung wall. Long term it is bad, many people are on oxygen for life. It also affects mostly women, and is likely woefully under diagnosed.

Well, at least for the kind of de novo mutation that the article is talking about, it's vanishingly unlikely that anyone has the same exact mutation. It looks at a cursory glance like the gene in question is ~180k base pairs long, so the idea that someone else also has this (potentially fatal) truncation in the same spot is really unlikely. Especially if the mutation would be fatal if it were misplaced a bit.

It's also a bit of misdirection, since the net effect is "half of your PLCG2 expression is turned off", which is probably also represented in that 60 similar patients the article talks about. So it's technically true but almost certainly something that other people have as far as a "half knockout of gene XYZ".

Ideopathic is latin for fucked-if-I-know-itis.

I've got at least two ideopathies going on and some friends with chronic pain that nobody can figure out. It sucks.

We probably need to test people for toxins in their systems. We are all probably running around with enough of five different things in our bodies that if you swapped them all for one you'd end up in the ER. It's just enough that you feel 'yuck' three different ways but aren't dying.