ME Diagnosis and Genetic Testing and also, Gratitude

[JaimeS]

So I've been lurking for months and posting for a few weeks, but this is the first post I've started myself, about myself. Here goes:

I found a brilliant GP in my area, and I don't think I have to tell you guys what that feels like, to have someone willing to listen, debate it out - like, we argued in a friendly manner over things! She told the receptionist on the way out the door, "make sure she always gets the last appointment of the day so we can talk as long as we want." She took the Canadian Consensus document I gave her and was absorbed in it AS I LEFT. <3 If I'm right about her, she's going to soon be the first doc in the mid-Ohio Valley to understand ME.

But clearly she doesn't know ME yet. I'm the first patient she's ever seen who's discussed it. I don't think she'd be comfortable diagnosing it. So my first question is: who would you recommend as a diagnostician for ME? I live in the continental US, Eastern/Central (mid-Ohio River Valley area) but I would be willing to travel pretty far to find someone who is good at neuroendocrine diagnosis in general and ME diagnosis in particular. (I went to the Mayo Clinic, which is over 800 miles away, so.) I did look at the Chronic Fatigue Roadmap, but I'm not sure who's best for diagnosis, and who has a rep for just giving everyone who walks through the door a protocol, already assuming they have ME... or who's a little ME-happy and doesn't bother to rule other things out quite as much as they should.

The second thing I wanted to ask you all about is genetic testing. My new GP told me that she wanted my entire genome analyzed in order to provide evidence for what is screwed up where. I immediately thought of Kerr's article and was super-excited to see if this could be done. Does anyone know if it's possible within the US healthcare system to get a test done that is so broad? My doc was educated in Ecuador and still seems unfamiliar with some of the types of tests that are and are not available here. When I search online, I keep getting places that do paternity tests. Not exactly what I was looking for.

Ideally I could find a genetics doc willing to consult with me (or even my new GP) via phone, have him/her write up an order, and get the blood drawn locally and sent off wherever it needs to go. Do you guys know anybody to recommend for that sort of thing? Has anyone here had anything like that done?

Can I close by gushing? I'm a research-y type who kept reading and searching until I knew as much as I could know about what was going wrong in my body. The more I researched and the more specific my inquiries became, the more often Phoenix Rising popped up in my google searches. I'm consistently blown away by how intelligent, educated, thoughtful and bloody-mindedly persistent you are as a group. Bitter and angry posts, which I would expect to be sky-high given our situation, are the exception rather than the rule. I've been grateful a dozen times over for the places you've sent me for research, especially in the case of the more prolific posters. Thanks for being here. If you guys ever have any questions about alternative medicine / herbs, let me know. That's my training.

Edit:

Additionally, we wanted to do anti-cortisol antibodies and anti-serotonin (and serotonin precursor) antibodies. I'm pretty sure if I knew of a lab that does either of those as a test, she'd find it and order it, but I keep finding Rabbit Anti-Serotonin Antibody for sale when I try. If anyone knows of a lab that does this sort of test, I would really appreciate a reference. <3

Edit 2:

On the advice of a member, I took the doctor's name down. I certainly wouldn't want someone to say she was being discussed and implying that it was in a negative way; nor would I want people calling/bothering her, as she certainly isn't an expert in ME at this point.

-JS

 

[helen1]

@JaimeS Welcome to the forum!
As far as recommending a diagnostician, have you looked into Dr Byron Hyde in Ottawa Canada? His two specialties are brain scans as Hip notes in his Roadmap but also ruling out other conditions or diseases. He's very good at that. Limited in his clinical work though in my experience.

I do have some questions for you about herbs. I'll PM you.

 

[JaimeS]

@helen1 Thank you so much! Very glad to be here. I look forward to hearing your questions, too!

I actually just tried to (audaciously!) write to Kerr and say, "listen, do you still need more genetic data, because here I am and I want it done" lol. The email bounced back saying it was undeliverable; I've since heard he's been banished from his original institution, so the email address clearly no longer works...

Canada is pretty far from where I am, but I was considering Dr. Hyde anyway as well. He seems to have a good rep. I'll search around for his name on the forum, see what people think.

-J

 

[WoolPippi]

hi

your best bet is to get your genome tested as a private person, via 23andme.com, and do the interpretation of the results yourself together with your GP. There are some sites that will help. 23andme will cost about 100 dollars.

that way you'll have all the information and will be able to navigate through the various interpretations and uncertainties that characterize the medicinal field/practitioners. And DNA knowledge. There's very much haystack from which we need to build our own puppets.

What I'm saying is that it's best to have the data and interpretation of it separate. Pretty much the same as with regular blood work results which ought to be given by a lab separate from their interpretation. Instead they mostly say: "you're within range" and our doctor concludes: "therefor you are not ill".

But they both forget to mention the range they use for interpretation and most times it is not suited to interpret the results. For example progesteron results are interpreted with a range that includes male 20 yo. Or they forget to mention you are systematically at one end of the scale. Or they just give back results one by one instead of combining them into a whole picture (thereby missing sub-optimal fuctioning of any organ)

Working like this helped me figure out my personal signature of this illness and I'm doing better for it

PS thank you for writing in paragraphs with white space between them
PS2 to make clear that 23andme will provide you with all the raw data from your genome. You get it and then you can look up any gen and see what your alleles are on that one.

 

[Valentijn]

@JaimeS - There are a few options for genetic testing, but I doubt insurance would cover any of them.

23andMe is the cheapest, at $99, but it only tests about 600,000 SNPs out of the 3.2 billion on the entire human genome. It doesn't test for a huge amount of of the SNPs known to cause diseases.

"Whole exome sequencing" is available for $1,300 from https://www.genebygene.com/pages/research# . Exome sequencing provides data from the protein-coding sections of the DNA, and is home to an estimated 85% of pathogenic mutations. That should be showing data for about 30,000,000 SNPs, or about 1% of the entire genome. You might be able to get exome sequencing done elsewhere for about half of that price, since you have a doctor willing to order it.

Getting the entire 3.2 billion SNPs on the genome tested would cost $7,400 at the same site . So it's costing about $6,100 to get the extra 15% of potentially disease-causing SNPs.

Personally I'd go with whole exome sequencing, if cost is of any concern. Though 23andMe is good value for the very low cost, and can definitely be helpful.

 

[JaimeS]

@Valentijn @WoolPippi

First of all, thanks so much for responding!

I'm worried about 23andMe because when you go there now, an alert message pops up that says they don't provide genome info for medical purposes. I suspected they might just give you raw data that they want you to take to a physician, but I worried I'd pay and get just information about my ancestry which, while interesting, is not exactly what I'm looking for.

This error message is dated from the end of 2013 (December?) so I'm not sure if you guys have made use of the service after that date or not. If someone here has gotten their data within the past year and can let me know that's the case, that would be awesome.

I found this at Illumina, where Kerr had the DNA analyses done in the 2014 paper. It looks like the same service is offered (complete exon), but it also looks like it's geared towards researchers and that may have an affect on price. I'll ask for a quote.

Instead they mostly say: "you're within range"

On looking more closely at my bloodwork from Mayo, both my IgG1 and IgG4 are below range... if you apply Quest Diagnostic's reference range rather than theirs. You really do have to be so vigilant to begin to get any idea of what's going on.

But they both forget to mention the range they use for interpretation and most times it is not suited to interpret the results.

Haha, I also found that when Mayo took blood to analyze lactate, they put the reference range for venous blood, when they'd drawn from arterial blood (which has a different reference range entirely!) I remember it was arterial because of them lidocaining my arm and poking around in there for fifteen minutes trying to hit the artery, before my exercise tolerance test. Not something you forget in a hurry.

Perhaps I can get insurance to pay part of that $1300... otherwise, good lord.

Thanks for the advice, guys. I appreciate it so much.

-J

 

[Valentijn]

I'm worried about 23andMe because when you go there now, an alert message pops up that says they don't provide genome info for medical purposes. I suspected they might just give you raw data that they want you to take to a physician, but I worried I'd pay and get just information about my ancestry which, while interesting, is not exactly what I'm looking for.

They never really had useful interpretations for medical purposes there. But if you know what you should be looking for (certain genes which are likely culprits), then it's pretty simple to look up your results on OMIM or dbSNP. I've also got a downloadable program at http://sourceforge.net/projects/analyzemygenes/ which will pull out your rarest results for you. It doesn't get everything, such as if there's no frequency data for a SNP, but that can still reduce the legwork considerably.

 

[JaimeS]

@Valentijn - thanks again! That is an amazing program; it looks like you co-authored it? I'm really impressed.

I did ask for that price quote at Illumina. I'll post here when they respond. I picked 'researcher' when they asked who I was - because that's who I am, right? Starting in a couple of weeks, I'm officially going to be working for a university again (from home), my old alma mater. And I plan on doing a lot of research on ME there, so....

-J

 

[WoolPippi]

@Valentijn @WoolPippi

First of all, thanks so much for responding!

I'm worried about 23andMe because when you go there now, an alert message pops up that says they don't provide genome info for medical purposes. I suspected they might just give you raw data that they want you to take to a physician, but I worried I'd pay and get just information about my ancestry which, while interesting, is not exactly what I'm looking for.

-J

on the site you can access the raw data. You can download it and do with it whatever you want. I put mine in a .txt and ran it through genomegenie and Valentijn's thing and a bunch of others.

or you can browse the data online on 23andme which looks like this on my screen:

You can browse by gene. Or you can search for specific SNP directly. It's really informative. (I don't show you any search results because I don't want my genome info on the net)
On the left, which I did not include in the screenshot because it shows my username, is the button to download the data.

The pop up message you read is about the fact that they cannot claim responsibility for any health remarks they previously made. It's a lawyer thing and like Valentijn said, it wasn't much to begin with. It did tell me I'm vulnerable to Warfarine and heroine. So there's that
It did check for a lot of heridatary diseases which is good to know for some people. But at our age most of those diseases will have revealed themselves, I guess.

I ordered the kit before the lawyer restriction was done but I strongly believe they still provide you with the raw data. It's part of how the site functions. In the forums there are plenty people discussing their SNPs and I'm sure many are from after the stop on health interpretation. To be absolutely sure you can always email them. As you see from the screen shot the words they use is "Raw Data".

 

[JaimeS]

So, because I know many of us have focus issues, I'm hoping it's okay to reiterate the information I'm still looking for?

• Additional doc recommendations for a diagnostician, although Hyde really seems to be the dude, doesn't he?

• Any lab that does tests for antibodies to serotonin or cortisol?

As far as the latter goes, someone recommended I find labs important to CFS/ME, call the lab, and ask who typically orders the test locally. I think they meant this in a general rather than specific way, so I'm kind of passing this information on because it's a really excellent, out-of-the-box way to find a good local physician.

However, in this particular case, the issue is that I can't even locate a serotonin antibodies test. I pulled up a bunch of laboratories from the ME roadmap and looked, but still no dice. This strikes me as super-odd, because I keep seeing serotonin antibodies discussed in the literature; but it doesn't seem to have made its way to clinical practice, yet. Or, not so far as I can tell.

@WoolPippi - I know that the one Valentjin recommended for $1300 is probably even more extensive, but it seems like 'only' 600,000 bits of data is already amazing/overwhelming. Thanks so much for sharing what you get from 23andme.

Thank you, thank you, thank you to everyone who has replied. <3 You guys are the best.

-J

 

[JaimeS]

For anyone who looks here later, it is also apparently possible to get not just your DNA raw data but to purchase a complete analysis package as well. This is the text I received from Illumina on inquiry:

"Dear Jaime,

"Thank you for contacting Illumina. We have two different tests for patients wishing to undergo whole genome sequencing (WGS) and I will provide a brief introduction to both. If after reading this information you would like more information regarding one of our tests, please let me know.

"The first test is our TruGenome Predisposition Screen. Our Predisposition Screen is geared toward healthy adults and is focused on adult onset conditions and carrier status. With this test we interpret 1691 genes which are associated with approximately 1232 disorders.

"The second test, our Undiagnosed Disease Test, is focused on diagnosing rare genetic disease. There are two ways in which WGS can be used to help in diagnosing rare disease. One way is to test a patient and their parents together. This allows us to identify and rule out genetic changes based on the pattern of inheritance we see between the three family members. The second way is to test an individual and narrow down the interpretation to genes that are associated with any of the symptoms they have. The family testing, called trio testing, is often the most informative type of testing, however it is also more costly than individual testing.

"Currently testing for an individual (Predisposition Screen or Undiagnosed Disease Test) is $9,500 USD. The price for the trio for the Undiagnosed Disease test is $17,500 USD. Results for any of the tests take up to 90 days. Whole genome sequencing must be ordered by a physician, and the results will be reported directly to the ordering physician. If your physician is not familiar with our test we would be happy to answer questions and provide guidance. Additionally, for a diagnostic test we strongly recommend you speak with a genetic counselor or medical geneticist to ensure that the test being ordered will be helpful for you.

"It is important to know as well that we do not bill insurance companies directly. Payment is required prior to the test being run. Patients may seek reimbursement from their insurance companies, and reimbursement varies depending on the insurance company and the indication for testing.

"I hope this information is helpful. I am happy to answer additional questions so please do not hesitate to contact me."

 

[JaimeS]

@Valentijn

So, my 23andme results came!

I may have this issue solved eventually, but I'm feeling brain-foggy and awful rn, so I figured I would ask you guys for help. Valentijn, I downloaded my results and your program. Then I downloaded the files saying "ten percent" and "one percent".

When I run the program, it's easy to enter my results into the little box asking for them. But when I look for either of the two databases, the program won't find them. In fact, ALL my folders disappear, when looking for databases. I placed both files in my Documents Folder, but when I click on 'Documents', nothing shows up in the display box at all, despite the fact that I have many folders there. I am sure this is where both files are located, but they do not show up.

This is probably something lame that I'm not seeing? I hope.

Thanks in advance for any help you can provide; and if you'd rather I deleted this post and wrote it on the program's page, that's cool too. However, I saw there were no comments or discussions there, and wondered if you'd see it in that location.

-J

 

[Valentijn]

@JaimeS - The one_percent and ten_percent should be in the same folder from which you run the program. They all need to be unzipped.

If that's not helpful, are you using a Mac? They can have some problems with programs aren't registered with them, and we aren't registering it because it costs too much.

And if that doesn't help, could you post or send me a screenshot of the folder with the one_percent and ten_percent files in it, and/or a screenshot when you try to go to the folder via the program?

 

[JaimeS]

@Valentijn - I made sure both files were in the same folder as the program. They are all unzipped.

I am using a PC.

Therefore, I've sent you a screenshot that shows the file that contains the program, my dna file, and the databases, and the empty box swearing I have absolutely nothing in my Documents folder at all....

 

[JaimeS]

Oh. My. Stars!

I had unzipped it, BUT I WAS STILL LOOKING AT THE FOLDER WHERE THEY WERE ZIPPED.

...fml.

Thanks for your patience, @Valentijn ...

My 23andme tells me I am 48% Ashkenazi Jewish. I expect this means I will have five hundred "less than 1%" ers.

-J

 

[Gondwanaland]

I worried I'd pay and get just information about my ancestry which, while interesting, is not exactly what I'm looking for.

My 23andme tells me I am 48% Ashkenazi Jewish. I expect this means I will have five hundred "less than 1%" ers.

Your ancestry turned out to be much more than interesting and quite a significant information!

 

[JaimeS]

@Gondwanaland - No kidding! My dad's side of the family is Jewish, but I never imagined they'd belong only to the group that was most genetically isolated and carries the most diseases. It looks like back in the 1800s someone on that side of the family married someone with varied Far Eastern Ancestry - equal parts Japanese, Chinese, and Indian - but they are otherwise completely Ashkenazi Jewish. (Which is, in and of itself, a melange of Middle Eastern and Franco-German, so...)

Still. All the living Ashkenazi Jews are descended from the same 330 people. That is astounding to me.

-J

 

[JaimeS]

@Valentijn @WoolPippi @Gondwanaland ...

...according to my methyllation data, I should be dead. Crazy, first - then dead.

Also, seriously - if no one minds saying, how many "unusual" less than 1% results did they get back? I'm curious as to whether my Ashkenazi ancestry has any impact on the numbers, or if the results I got back are 'the usual'. I seem to have about 100 of them. Is this about what everybody gets?

-J

 

[Valentijn]

...according to my methyllation data, I should be dead. Crazy, first - then dead.

The Yasko methylation SNPs (also reported by Genetic Genie) get way overblown. Most have very little or no impact, heterozygous mutations usually have no impact unless they're compound hetero missense mutations, and the missense mutations which have a significant impact are very common in the general (healthy) population.

Also, seriously - if no one minds saying, how many "unusual" less than 1% results did they get back? I'm curious as to whether my Ashkenazi ancestry has any impact on the numbers, or if the results I got back are 'the usual'. I seem to have about 100 of them. Is this about what everybody gets?

On the newer (V4) chip, I think 60-100 is pretty normal. On the older V3 chip, 130-150 seems typical.

 

[JaimeS]

I don't really know how seriously to take it all, @Valentijn, but I really was being tongue-in-cheek about the crazy stuff. I'm homozygous for:

COMT V158M
COMT H62H

VDR Bsm

MAO A R297R

MTRR A66G

CBS C699T

I know the heterozygous results are less important, but reading up on a few of them individually, some cause enough of a change in the gene expression to be significant:

MTHFR C667T
MTHFR A1298C
MTRR A664A
BHMT-08

I also got 'no call' on CBS A360A. Not 'not genotyped' - 'no call'.

@WoolPippi has an interesting chart over @ another post I'm going to look at.