Good Lord, People, 23andMe is NOT Dead!

23andMe

Good Lord, people, 23andMe is NOT dead! Or closed, or no longer taking orders, or anything like that. I hear this a lot.

“You know, I always wanted to get my genome tested. I was going to try 23andMe, but then the FDA shut them down. Oh, well, missed my chance. [sigh]“

NO! You did NOT miss your chance. Firstly, 23andMe is not closed for business. They still will take your money and your sample. They still will analyze the sample and give you results. From what I’ve been seeing in the results from folk I’ve been helping to look at their data, 23andMe seems to be running the test exactly the same way they always did, for the same SNPs.

They simply are, at this time, not offering their health reports to new customers. It isn’t the data that has changed – it iw what analysis is shared with the customer. Old fogies like me who got their tests done before the FDA folderol” still have access to our old 23andMe health reports, and they continue to improve them.

I have heard nothing to indicate that 23andMe are not working with the FDA to try to make it possible to release health reports again in the future. Issues around that get complicated and I’m going to save them for a later post. Right now, what if you wanted a test for some genetic health information? Can you do it? How long will you have to wait to find out the answers to your health questions?

You can still do it. It isn’t as easy as it was before, but it can be done. I’ve been spending a lot of time talking people through how to do this, and it is time to write it down. If nothing else, it will save me time. This will be the short short version, and I can answer more detailed questions and describe specifics, maybe give an example or two or three.

FIRST, THE DISCLAIMER

Risk is Not Just Genes

Making sense of genetic information is complicated even for experts, which most of us are not. Of course, part of the irony of looking at genetics for health conditions is that most of the time what causes the condition is not just the genetics, but genes PLUS something else. If you don’t find the genes for something, that doesn’t mean you can’t get it; if you do find the genes for something, it doesn’t mean you will get it. It is hardly ever a case of this=that.

What Does Risk Mean, Anyway?

There is also the challenge of figuring out how important the risk is, and whether or not to do something about it. So, my personal risk of celiac disease is over 4 times normal. Wow! That sounds like a lot, doesn’t it? But 4 times normal for celiac risk is still only 1 in 20 people, because normal is about 1 in a hundred. I know someone with celiac risk 17 times normal, which is 1 in 4 people. That’s getting to be pretty serious! But, while celiac is dangerous, it isn’t one of those conditions that is immediately deadly or painful. And my friend still has a 3 in 4 chance of NOT getting celiac, and that is a lifetime risk.

On the other hand, my risk of venous thromboembolism (VTE) is 1.5 times normal. That doesn’t sound like much does it? It’s higher, but only a little bit. So we don’t really need to worry about it, do we? Well, yes. VTE can kill you on the spot, and it is incredibly painful. And normal is 1 in 10 people for lifetime risk. For me, the risk is closer to 1 in 7.

Given that, according to 23andMe, my genetic risk of celiac is roughly 1/20 and my risk of VTE is 1/7, and adding in the comparative dangers of the two diseases, my docs got all excited about the VTE, and not terribly about the celiac. I hope you understand why now, and also a bit more about why genetic risk is complicated.

On Asking for Help

Last part of the disclaimer.

For both of these, celiac and VTE, 23andMe looks at SOME of the genes and SNPs known to be associated with the condition, but not ALL of them. So whatever 23andMe tells me about risk is only part of the picture. It looks at the most important genes, but is still only part of the picture. That’s why you need experts to put all the pieces together, and get more information to fill in the gaps from the 23andMe test.

Everyone always says, “Ask your doctor,” when it comes to finding something puzzling, confusing, contradictory, or worrisome in your genetic tests. I did, and found that most of my doctors didn’t have the expertise to make more out of it than I did. Some poohpoohed the 23andMe results, others made clinical decisions based on them without verifying with other tests, some asked for more medical tests to expand upon what 23andMe had, and one said, “You know more about this than I do, but I’m going to learn.” Here is a quote from an NEJM article a few months ago about the risks and benefits of trusting direct-to-consumer personal genomic services such as 23andMe.

“Clinicians will be central to helping consumer–patients use genomic information to make health decisions. Any regulatory regime must recognize this reality by doing more than simply adding the tagline on most consumer ads for prescription drugs: “Ask your physician.” That is insufficient guidance unless your physician has ready access to a clinical geneticist or genetic counselor.” Annas GJ, Elias S. 23andMe and the FDA. N Engl J Med 2014; 370:985-988. http://www.nejm.org/doi/full/10.1056/NEJMp1316367

Some of the personal genomics service offer phone-in access to genetic counselors. I tried that, and didn’t get helpful answers there, either. Even worse, one of the answers I got was blatantly wrong. It may have been just the genetic counselor who I happened to be talking with, so don’t judge the whole profession by that one person, but do be prepared to keep looking for info if needed. Where I found the most helpful information was in the 23andMe forums, BUT a lot of the info there was unreliable, and I had to sort out what was helpful and what wasn’t.

So, my recommendation is, absolutely DO ask your doctor, ask a genetic counselor if you can, but that might not be enough. You might need to do more research on your own, or find someone you trust to help you with this.

What Good Is It?

So, what good is it then? It gives you clues. Like a detective, you take the clues and look for more information, or ask for more thorough testing, or raise questions that weren’t being asked or addressed before. Some of the clues will be red herrings. Some of them may lead you to a prized solution. For me, these clues ended up dramatically improving my quality of life, and may have even saved my life.


So, now, the short short version. And PLEASE, if someone more expert than me with genomic data reads this and spots any errors, please say so!

PART ONE

1. Get your 23andMe test done.

Pic of the Day - PGenPGEN, Take 2

2. Log in at the 23andMe web site when you are notified that your results are ready.

23andMe

3. Click: Browse raw data.
23andMe: Getting to your raw data

It should look like this:

23andMe: Browse Raw Data

4. Click: Download raw data.
23andMe: Download Raw Data

5. Complete security procedure (log in again, answer security questions, etc.). It should look like this.

23andMe: Downloading Raw Data

6. Answer the question about what type of data and format you want. NOTE: I always choose ALL DNA, unless you have something else specifically in mind.

23andMe: Downloading ALL Your Raw Data Or ...

7. Find the file (which will be named something like genome_Firstname_Lastname_Full_12345678901234.txt)

PART TWO (A): Easier Way

Genetic Genie

Now you have choices. You can dig into the information the easier way, or the less easy way. Let’s start with the easier way.

1. Select a tool to do what you want with your data. There are LOTS of tools people have built to do useful things with 23andMe data files. One of my favorites is Genetic Genie, because it tells you about the MTHFR gene which has become so important in my life. I also am spending a lot of time with Promethease because it is so complete compared to most other 23andMe analysis tools. Lets start with these.

2. Go to the tool of your choice, such as:

Genetic Genie: http://geneticgenie.org/

Promethease: http://www.snpedia.com/index.php/Promethease

3. Follow the directions at the tool, but this almost always requires you to upload your 23andMe data file. Here are more details about doing this with Genetic Genie.

4. Last come what is always the tricky part — making sense of the information you get. That’s worth several posts, but for starters the main point to remember is that the 23andMe test is a place to start, not a final answer. In Genetic Genie, the code, analysis, and text are written by engaged amateurs, not by doctors or genetic counselors. They worked hard, collaborated with a lot of other people, and did a lot of research, but it isn’t going to say the same things your doctor might.

More Tools

23andMe: Tools for Everyone http://www.23andyou.com/3rdparty
NOTE: When 23andMe took out the health reports, they also edited this page to remove links to tools that provide health data from 23andMe data. So, this is interesting and useful, but not sufficient. You’ll have to look somewhere else for most tools.

23++ Chrome Extension: Get more from your data:
http://23pp.david-web.co.uk/getting-more-from-your-data/

Confessions of a Cryokid: Top 10 things to do with your FTDNA raw data (2011) http://cryokidconfessions.blogspot.com/2011/06/top-10-things-to-do-with-your-ftdna-raw.html

Genetic Genealogist: What Else Can I Do With My DNA Results: http://www.thegeneticgenealogist.com/2013/09/22/what-else-can-i-do-with-my-dna-test-results/

International Society of Genetic Genealogy: Autosomal DNA Tools: http://www.isogg.org/wiki/Autosomal_DNA_tools

Resqua: Q: What should I do after generating my Gene variance report? http://resqua.com/100005927200207/what-should-i-do-after-generating-my-gene-variance-report

Think Exponential: Get SNPd! http://thinkexponential.com/2013/01/10/why-you-should-get-snped/

PART TWO (B): Less Easy Way

Linking Disease Associations with Regulatory Information in the Human Genome

Actually, there are a LOT of different “less easy ways.” You can open the raw data file in a text editor and search manually for specific pieces of information. Or, if you code, you can write a little program to do some of the hard work for you.

Basically, it comes down to doing a lot of research, the hard way, by hand. But, believe it or not, I am doing it. I’ve had a lot of help from people who offered tips or comments in the 23andMe or MTHFR.net forums, on Facebook, on Twitter, and comments on these blogs. I am NOT an expert, but like most readers of this blog, just someone who wants or needs to know more. This is what I’ve learned and figured out on my own, offered as an example, nothing more.

Critical Background

23andMe gives SNP-based data. SNP stands for single nucleotide polymorphism. Polymorphism means something that can be itself but in different ways, our eyes are eyes whether they are blue or brown or hazel or violet or any other natural eye color. I won’t give an introduction to genetics here, but there are several online resources that explain these ideas, with one of the best resources being Genetic Home Reference from the US government. Depending on how much you want to know, you may wish to take the Coursera courses Introduction to Genetics and Evolution (Duke U) or Experimental Genome Science (U Penn).

1. What SNPs do you want to know about? Check here:

RegulomeDB (Stanford): Linking Disease Associations with Regulatory Information in the Human Genome: http://regulomedb.org/GWAS/

I have also found SNPs of interest in research articles, PUBMED, and other places, but this is a good start. The SNP identifier (what you need) will look something like this:

rs2187668

2. Find out which polymorphism is the one considered “healthy” or “normal”, and which one is the one associated with risk of disease? These maybe called “risk alleles” or
simply polymorphisms.

For example, for SNP “rs2187668″ (one of the celiac risk SNPs) the risk indicator is (T), while the normal is (C).

3. Open your 23andMe raw data file in a text editor, like WordPad (Windows) or TextEdit or TextWrangler (Macintosh).

4. Search for the SNP you want to know about. The data will be in four columns:
– RSID
– Chromosome
– Position
– Genotype
You need to know about the first and last columns, RSID and Genotype. It will look a little like this.

rsid…..chromosome…..position…..genotype
… [many other rows of data] …
rs2187668…..6………32605884…..CT

So, this person (me) has for that SNP one risk allele “T,” (which I happen to know is from my dad, by comparing it to his scan) and one normal allele “C,” (which must, by default, be from my mom, since for every gene pair we have gotten one from each parent).

5. Repeat for all the other SNPs associated with the condition you are researching.

6. Search for more information and articles about those SNPs, the condition, and more. You can’t make sense of this without more information. And ask lots of questions.

More Tools

ENCODE:
About: http://www.genome.gov/encode/
Data: http://genome.ucsc.edu/encode/

ENSEMBL Genome Browser: http://useast.ensembl.org/

OpenSNP: https://opensnp.org/ OR https://opensnp.org/snps/

SNPedia: http://www.snpedia.com/

UCSC Genome Browser: http://genome.ucsc.edu/

Trying Out SAM-e (Smart People Can Do Dumb Things)

Screen Shot of image search for SAM-e

Another girlfriend suggested SAM-e, and since it connects to methylation and we know I have mega-MTHFR challenges as well as other methylation problems like COMT, I figured I’d give it a try. Before you read too far, the end of the experiment for me is a big fat “NO, DON’T DO THIS.” But, of course, it isn’t that simple. I’m still not feeling well, so I’m trying to keep this simple. In part, this is an example of how to research something before you decide on a new course of treatment for yourself, and in part it is a cautionary tale.

WHY I THOUGHT IT MIGHT HELP

What is SAM-e used for? The big ones are depression, osteoarthritis, fibromyalgia, and liver disease, but these are also mentioned.

ADHD
anti-aging
Alzheimer’s
anxiety
back pain
bursitis
chronic fatigue syndrome (CFS)
dementia
depression
fibromyalgia
heart disease
lead poisoning
liver disease
migraines
multiple sclerosis
osteoarthritis
Parkinson’s
premenstrual dysphoric disorder (PMDD)
premenstrual syndrome (PMS)
seizures
tendonitis

Well, with a list like that, I figure a lot of folk think the same thing I did: “Gee, several of those apply to me or my family. Who knows? Maybe it might help. Let’s give it a try.” The first piece I looked at clustered these into categories of (1) bone and join problems, (2) nervous system problems, and (3) organ health. Two of those are themes in my life, so it was making sense that it might be part of the picture. And I really really wanted to feel better.

WHAT I RESEARCHED BEFORE TAKING IT

No, I’m not so foolish as to simply dive in and start taking something on a whim. Everything we ingest can have effects like a drug; everything has a minimum and maximum recommended dose; everything has interactions and side-effects, indications and contraindications. I looked it up, in major drug databases as well as Google Scholar, Pubmed, and some drug databases. I looked for the interactions and side-effects (there are LOTS). I looked at signs of an overdose. Turns out there are two kinds of overdose: (1) over-methylation, which makes you jittery, anxious, sleepless, etc.; and (2) serotonin syndrome, which can be fatal, and starts out with agitation, restlessness, confusion, tachycardia, high blood pressure, muscle twitches, sweating, diarrhea, headache, shivering, fever, goosebumps.

I felt pretty prepared at that point, but there were a few more things I wanted to know. The importance of SAM-e in the methylation process was obvious with even a superficial web search. Since I have MTHFR deficiency and that is also a big problem with the methylation cycle, I wanted to make sure the two don’t interact in nasty ways. So I searched for information about interactions between SAM-e and methylfolate, warnings, precautions, etc.

This was more interesting. First off, it turns out that methylfolate helps people make their OWN SAM-e! They are part of the same cycle, and SAM-e is one of the by-products from MTHFR processing. Regarding taking both, there was virtually no solid evidence floating up to the top, but an awful lot of opinion and personal experience. (Guess I’m adding to that body of unclear literature.) I saw a lot of people saying, “If you have MTHFR deficiency, do not ever take SAM-e!” This was balanced by an equal number of folk saying the opposite. The overall picture was unclear. There was a lot that said to take them together, almost nothing about if you have an MTHFR deficiency.

I found one woman who described it as helpful for brief periods, and she described her genetics as similar to mine — heterozygous MTHFR, homozygous COMT (H62H & V158M), and celiac. She described reacting with an over-methylation response after a couple weeks, and I had gone through that when I started taking methylfolate and felt I know what to do. Just to be careful, I started out with the smallest dose I could find – 200mg.

WHAT HAPPENED

Part of what was motivating this was that general feeling of being unwell that I’ve had ever since I returned from my trip. I really want to feel better, but am feeling crummy. I thought about waiting to start SAM-e until I feel better, but based on what information I’d found I thought I knew what to expect. Either it wouldn’t do much, or I’d feel better.

I took a half dose on Monday. I felt basically the same as I’ve been feeling — generally crummy. Tuesday the same thing. I wasn’t sure if I’d been glutened or not. I took a couple days off, just to see. Then I thought maybe I hadn’t taken enough to notice a difference. [The problem with this was I had forgotten to look at how long it takes to feel an effect, and it varies depending on the problem.]

I was taking Friday as vacation, and thought I’d risk taking a larger dose, since I didn’t want to experiment if I was going to try to work. Instead of 200, I took 400. I continued to feel vaguely crummy, and then I started to feel as if I’d been glutened. I’d been eating “whole foods,” so I couldn’t imagine what it would have been, but I recognized the feeling. Fatigue. Brain fog. Wobbly. But not a hint of any digestive symptoms, no bloating, no hives. I was puzzled, but sleeping too much to figure it out. I had trouble sitting and standing, my joints hurt. I felt too weak to do much. Not normal symptoms included feeling hot, sweaty, feverish, flushed, confused, congested, chilling, spaced out, distractible. Then I got a headache, and my head feels strange in the back. So far, this has lasted three days. Each day has had a couple brief periods when I felt ok, before it would start up again, slightly milder than the day before.

WHAT I LEARNED AFTERWARDS

I went back and looked again at SAM-e overdose. Nope, these symptoms don’t match up, except for the headache. My symptoms were more like those indicators that someone needs more SAM-e. Very puzzling. I kept digging into literature about SAM-e. I tried taking extra methylfolate, but didn’t notice a difference. I did notice that my clear-headed time was in late afternoon, and every day I take a B-complex vitamin with my lunch. Then I stumbled into some information that SAM-e can cause problems if someone is deficient in B-vitamins (like me). Basically, it creates a lot of homocysteine, which the body can’t clear out because it needs more B-vitamins to do so.

I put 3 and 3 together. Maybe this was a SAM-e overdose, but my body couldn’t properly process the SAM-e? I tried taking extra B-vitamins to see if this helps clear the fog and confusion and fatigue. I’m not trying to do it all at once. I took a B12 and my usual B-complex, then waited a few hours and took another B-complex. So far it seems to be working. I’ll add an addendum tomorrow.

SOURCES

About.com, Alternative Medicine: SAMe, What Should I Know About It? http://altmedicine.about.com/od/treatmentsfromatod/a/SAMe.htm

Mayo Clinic: SAMe: Safety: http://www.mayoclinic.org/drugs-supplements/same/safety/hrb-20059935

Mayo Clinic: Serotonin syndrome: http://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/basics/definition/con-20028946

Natural Database: SAMe: http://naturaldatabase.therapeuticresearch.com/nd/PrintVersion.aspx?id=786

University of Maryland Medical Center:
S-adenosylmethionine http://www.webmd.com/vitamins-supplements/ingredientmono-786-SAMe.aspx?activeIngredientId=786&activeIngredientName=SAMe


UPDATE June 24, 2014:

Looks like I probably guessed right. The extra B-vitamins are helping, allowing me to get through the day. I couldn’t find anything about the length of time it takes to clear SAM-e from the body (personal reports range from on day to a couple weeks). I’ll probably have to take extra B-vitamins for a few more days.

Ingredients, Not ‘Food’

Checkerboard Egg CartonOnions

When I was in Chicago for my business trip, I was staying with my friend Rita. She was worried about how to feed me safely, since she isn’t gluten free herself, and since I am what many people have told me is “freakishly hypersensitive.” I told her what I’ve heard other people say, “Stick to whole foods.” But what is whole foods? What does that mean? It isn’t Whole Foods, the grocery chain, it means something different, although there is some overlap. You can say the other meme, “Shop the outside edge of the grocery store,” but that is lot riskier and more vague. I tried to explain, but I wasn’t doing such a good job. She figured it out, and when she did she said, “You know, this isn’t that hard!” No, it isn’t, but it is hard to explain.

Farmer's Market - Sept 6, 2008Making Preserved Lemons

After I came back from Chicago, there was a day I was riding back home from sword practice with my friend, Charles. He was telling me a story about when he was young and one of his friend’s came over to hang out and then got hungry. He told his friend to look in the fridge, and his friend complained loudly, “Where’s the food? You don’t have any FOOD in here, all you have is INGREDIENTS!” To which Charles replied, “Ah, but with ingredients, you can MAKE food.”

“AHA!,” I thought, “That is how to explain it!” The idea of “whole foods,” what is my primary foods, what I usually eat, is actually made up of things that many other people don’t even think of as food. That was a revelation and a hard idea to wrap my head around. Kind of like talking different languages.

Pic of the day - Not Cucumbers, Not SquashOkra

While in Chicago, I was fine as long as I was at Rita’s, but I got into trouble that last day of the trip, after I left Rita’s and was traveling home, eating so-called gluten-free food from restaurants. When I was so badly glutened in Chicago, for some odd reason, I just haven’t been able to shake it since I came back. I’ll feel better for a couple hours here or there, but then something else will set me back, and I’ll feel rotten again. It’ll be a month in two days, I’m very tired of this. I’ve been trying all kinds of things, some of which will turn into other blogposts, I hope.

The past few months I read both Grain Brain by Perlmutter and Gluten Freedom by Fasano. I’d hoped to do a quick review of each of them, but to avoid doing that here, let’s simply say I found Grain Brain frustrating and Gluten Freedom fabulous. One of the things mentioned by Dr. Fasano in his book was “The Fasano Diet” for people who are hypersensitive (like me) or seem to have gluten-induced symptoms no matter how careful they are (like me).

2013-07-06 at 10.12.45Farmer's Market - Sept 6, 2008

I was interested in trying it out, but I didn’t find the description in the book terribly helpful. I read a blogpost by someone who is a patient of Dr. Fasano’s and is on the diet to try to get some insight.

The Gluten Contamination Elimination Diet (Summary Of Dr. Fasano’s Recent Paper) http://www.celiac.com/gluten-free/blog/1038/entry-1780-the-gluten-contamination-elimination-diet-summary-of-dr-fasanos-recent-paper/

Frankly, this wasn’t much help either, but it did give a citation to the article for the Fasano Diet.

Justin R Hollon, Pamela A Cureton, Margaret L Martin, Elaine L Leonard Puppa, and Alessio Fasano. Trace gluten contamination may play a role in mucosal and clinical recovery in a subgroup of diet-adherent non-responsive celiac disease patients. BMC Gastroenterology 2013, 13:40 http://www.biomedcentral.com/1471-230X/13/40

The guidelines for the diet are listed in Table 1.

Table 1: Products allowed/disallowed in the Gluten Contamination Elimination Diet (GCED), targeting the elimination of gluten cross-contamination

Grains:
Allowed: Plain, unflavored, brown and white rice
Not Allowed: Millet, sorghum, buckwheat or other inherently gluten-free grains, seeds, or flours

Fruits/Vegetables:
Allowed: All fresh fruits/vegetables
Not allowed: Frozen, canned or dried

Proteins:
Allowed: Fresh meats, Fresh fish, Eggs, Dried beans, Unseasoned nuts in the shell
Not Allowed: Lunch meats, Ham, bacon; Other processed, self-basted or cured meat products

Dairy:
Allowed: Butter, yogurt (unflavored), milk (unflavored), aged cheeses
Not Allowed: Seasoned or flavored dairy products, Processed cheeses

Condiments:
Oils, vinegar, honey, salt
Flavored and malt vinegars

Beverages:
Allowed: 100% fruit/vegetable
Gluten-free supplemental formulas
Gatorade, milk, water

Hollon et al. BMC Gastroenterology 2013 13:40 doi:10.1186/1471-230X-13-40

I printed off the article, read it, highlighted, read it again. I still feel like the description just doesn’t answer my questions. They say in the article what criteria they use before putting a patient on the diet, what sort of problems patients had trying to stay on the diet, and that before starting the diet it is really important to consult with a dietician.

2013-07-06 at 10.53.492009 - Montebello's Rainy Day

Well. That’s nice. If I had a “real” celiac diagnosis, had had a biopsy, had a clue of the condition of my villi, then I might be able to get help with the symptoms, the ongoing challenges. I might be able to get someone to give me a referral. As it is, I’m on my own for a lot of this. So I’m trying to figure it out on my own.

Here are some examples of the types of questions I’m answering for myself. Please note, I DO NOT KNOW IF THE ANSWERS ARE RIGHT!

Q: No frozen meat?
A: Don’t buy it pre-frozen. You can buy fresh meat and freeze it yourself.

Q: No flavoured vinegars?
A: If you buy plain apple cider vinegar and fresh fruit or garlic, then flavor the vinegar yourself by soaking the flavoring fruit or garlic in the vinegar, since all of it is made from allowed ingredients, the result will also be allowed.

Here’s another example of my twisted flawed logic for trying to stumble through self-guidance for the Fasano Diet. Alright, rice is allowed. But rice makes me feel sick and quinoa makes me feel good. So, me, I’m using quinoa. Fresh chicken is allowed. Fresh onions. Fresh mushrooms. I can use salt. I can use butter. I can sauté the mushroom in butter with salt. I can grate “aged cheese” and use that (but should NOT use pre-grated cheese bought at the store). So then, I can make this, right? And this would count as “whole food” because all the ingredients were bought fresh and whole and then assembled into something by yours truly. And now I have food.

"Whole Food" sort of

On Getting Glutened

Field Training 2
Field Training 2; (US Army photo by Spc. Robert H. Baumgartner); 82nd Sustainment Brigade

People often ask me, “What is it like? What happens?” Some are sheepish or shy about asking, others are avid and openly curious, but either way they want to know. Sometimes they’ve heard it’s like having the flu, but don’t know that it can be different for different people.

Recently, I was traveling for the first time in a few years, and got badly glutened on the last day of the trip. it was the first travel day that I wasn’t able to make my own food, and had no choice but to buy “gluten free” food from restaurants. I will never know which food caused the trouble, but I do now remember quite vividly what my daily life was like before I went GF. I was trying to explain it to one of my best friends. The explanation went something like this.

“Imagine you’re a raw recruit in bootcamp. It’s the third day, and you’ve just realized this is going to be harder than you expected. Then the sergeant comes, and before you know you’re all suited up in 50 pounds of body armor, carrying two backpacks, and miles away from camp with no idea how long the hike will be. You’re dragging, trying to find a second wind, then crumpling; trying to find a third wind; a fourth …”

“I’m sorry,” said my girlfriend.

“No, wait,” I answered, “That’s just the beginning.”

“You realize you aren’t in bootcamp after all. You’re somewhere else, a forest or jungle or something. The weather is strange, hot, then cold. Or maybe you’re sick. You feel queasy, sweating and chilling at the same time. Somehow ants have crawled in under the armor, and they’re biting you, something fierce.

“And you’ve been drugged. You’re confused, not sure where you are, what you’re supposed to be doing, who you’re with. You just keep moving because if you don’t you feel like you’ll never move again. Your eyes keep closing, and half the time you are walking (stumbling, actually) with your eyes closed, catching a quick blurred glimpse, and falling closed again. But you are at least moving! Hey, that’s something to be proud of, right?

“And then you open your eyes. You’re in an office building, surrounded by people. You know you work with them, but you can’t remember their names. They are all looking at you, wary, like you just said something crazy or did something scary. You don’t remember. What did you say? What should you say? You shrug, grin lopsided, ask what’s next, as if it makes sense, and you pray that it does. But you still feel like you’re 200 pounds heavier and drugged.”

That’s what it feels like when I get glutened. How long did it last? This time was especially bad — around a week and a half. I managed to do what I needed to do for work, collapsed when I got home, made it through and made sense most of the time. And I am very, VERY grateful that this is no longer my everyday life. That it stops.

Alzheimer’s, Cognitive Impairment, & MTHFR Genetics

November Trip: Visiting Grandma:

It’s been over a year since I posted here. There are lots of reasons why. In that time, just to touch on the high points, my mother died and I suffered a major injury to my right arm which makes it hard for me to type and write and such. There has been so much happening in this space about which I really WANTED to write! The whole brouhaha with 23andMe and the FDA was a big one. There have been a number of interesting research articles that have come out. I did a presentation about my condition and meant to share the slides here. I may still, someday, write about these things.

For today, I want to talk about the research connecting genetic changes to the MTHFR gene to Alzheimer’s, Mild Cognitive Impairment (MCI), Vascular Cognitive Impairment (VCI), and related cognitive challenges. Because of my ongoing challenges with typing, I’m going to keep this simple, by selecting examples of the research and giving very brief snippets of the key findings. In other words, what’s most important.

The reason why I want to do this is because a friend of mine was recently diagnosed with one of these conditions, and so many doctors are not aware of this connection and don’t look for it. I’ve heard that from a number of places, but have a particular story that really rammed it home for me. As a medical librarian who works with systematic reviews, I’m on a number of medical and library email lists with various medical experts in different disciplines. On one of those lists, a clinician posted a question about this question. He is a recognized expert in his field and an expert in seeking and finding quality medical information. The family of one of his patients had approached him. Their mother has Alzheimer’s and they were wondering about giving her methylfolate supplements to help slow or arrest her memory loss. He wasn’t convinced, and was reluctant to support the family with this request. But he found enough evidence in support of the idea that he wanted to ask other professionals about the idea, and whether any of them had strong feelings about this. I sent him my search strategy and a few selected citations, and hoped for the best. I wondered, though, if someone as expert as he is was unaware of this, and reluctant to go along with a family’s request, what hope do others have with doctors who may very well not even ask the questions he was asking.

That was someone far away, in another country. I have no idea what happened. Now it is my friend, and I’m not close enough to talk with her clinicians. I’m hoping that someone will show this to her doctor, and if that doesn’t happen, maybe it will help someone else.

For the record, this is also a topic I follow because of personal concerns. When I was 12 I was briefly a significant part of my grandmother’s caregiving team. I was told at the time that she had Alzheimer’s, and it frankly terrified me. Years later, following brain damage from longterm carbon monoxide poisoning (another story for another day), I not only had amnesia but seemed to be developing mild cognitive impairment. It took me years to admit this to my doctor, and then brought it up at every appointment for the next few years. I won’t bore you with what didn’t work, but when I serendipitously discovered the MTHFR deficiency and began taking methylfolate, all my memory problems disappeared. Poof! Just like that. It was pretty amazing, and they haven’t come back. (Well, as long as I don’t get glutened.) Then, in the final part of her life my mother had cognitive decline. We don’t know her MTHFR status because we couldn’t get her genome tested, but we do know from testing other family members that she had at least one copy of the A1298c polymorphism. So, yes, I have a personal bias regarding this. That’s an excellent reason for me to stick to the evidence and what it says instead of trying to interpret it for you.

LOOKING AT THE RESEARCH

Context

There are several MTHFR variations which are considered potential problems. The big ones are C677t and A1298c, with newer and less well understood, the MTHFR 03 P39P. The SNPs (snips) for these are:
* MTHFR C677t = rs1801133
* MTHFR A1298c = rs1801131
* MTHFR 03 P39P = rs2066470
Each of these is associated with different health impacts. A study that shows that one of them does something (or does not) says absolutely nothing about the other variants. There isn’t enough research yet to look at all of them together across the board. For many of the MTHFR variations, one common association is for increases in homocysteine (hyperhomocysteinemia), which in and of itself causes much damage in the body.

The Search

So, to start off, here is the Pubmed search strategy I’m using to try to get to just high quality research on this topic.

(mthfr OR methylfolate OR L-methylfolate OR Methylenetetrahydrofolate OR 5-mthf OR l-5-mthf) (“alzheimer disease”[MeSH Terms] OR “Mild Cognitive Impairment”[MeSH Terms] OR “dementia, vascular”[MeSH Terms] OR “dementia”[MeSH Terms] OR “Cognition Disorders”[MeSH Terms] OR “memory disorders”[MeSH Terms] OR “amnesia”[MeSH Terms])

Today, that results in 121 citations. Since this topic actually has fairly deep roots in the literature, going back to at least the early 1990s, I’ll be selective and focus on newer articles. To be even more selective, I am limiting this to systematic reviews and meta-analyses, the very top quality evidence available, and only the most recent of those available in English. Systematic reviews and meta-analyses distill the best evidence available into recommendations for clinical practice. In other words, they look through the whole puzzle and say, “This is what doctors need to know, and what they should consider doing.” After that, I may add just a couple very new research studies that would not have been included in the reviews.

For me, I will say that while some of these show a strong connection and others only a weak connection, there aren’t any that show no connection or the opposite. The gathering of these large aggregated studies together confirms a solid connection in some populations and is suggestive that may not have enough data to know yet about other populations. If it was me or my loved one, I’d wonder if it is worth at least doing a test and considering possible low levels of supplementation with methylfolate as a low-cost, low-risk intervention, and then seeing how the patient responds.

SYSTEMATIC REVIEWS AND META-ANALYSES

2007
Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet. 2007 Jan;39(1):17-23.

In addition to identifying the epsilon4 allele of APOE and related effects, we pinpointed over a dozen potential Alzheimer disease susceptibility genes (ACE, CHRNB2, CST3, ESR1, GAPDHS, IDE, MTHFR, NCSTN, PRNP, PSEN1, TF, TFAM and TNF) with statistically significant allelic summary odds ratios (ranging from 1.11-1.38 for risk alleles and 0.92-0.67 for protective alleles).

2010
Laumet G, Chouraki V, Grenier-Boley B, Legry V, Heath S, Zelenika D, Fievet N, Hannequin D, Delepine M, Pasquier F, Hanon O, Brice A, Epelbaum J, Berr C, Dartigues JF, Tzourio C, Campion D, Lathrop M, Bertram L, Amouyel P, Lambert JC. Systematic analysis of candidate genes for Alzheimer’s disease in a French, genome-wide association study. J Alzheimers Dis. 2010;20(4):1181-8. doi: 10.3233/JAD-2010-100126.

We selected twenty genes from the “Top Results” list on the AlzGene database website and assessed their association with risk of developing Alzheimer’s disease (AD) in a large, genome-wide association study (using 526 SNPs from 2,032 AD cases and 5,328 controls) performed in France. The APOE, CLU, PICALM, and CR1 loci were excluded, since they had already been extensively analyzed. Ten genes/loci (TFAM, SORL1, CHRNB2, SORCS1, DAPK1, MTHFR, GWA 14q32.13, BDNF, NEDD9, and CH25H) showed weak nominal association with AD risk, in line with previous studies. In the remaining ten genes/loci (TNK1, ACE, CST3, IL1B, hCG2039140, PRNP, GAB2, LOC651924, IL1A, and TF), no single nucleotide polymorphisms were associated in our dataset. Of the genes showing nominal association in our cohorts, TFAM and CHRNB2 appear particularly interesting and warrant further genetic and functional follow-up analyses.

2010
Liu H, Yang M, Li GM, Qiu Y, Zheng J, Du X, Wang JL, Liu RW. The MTHFR C677T polymorphism contributes to an increased risk for vascular dementia: a meta-analysis. J Neurol Sci. 2010 Jul 15;294(1-2):74-80. doi: 10.1016/j.jns.2010.04.001. Epub 2010 May 2.

RESULTS: A total of 11 studies, comprising 672 cases and 1038 controls, were included worldwide. Publication bias was not observed. This meta-analysis demonstrated that the MTHFR T allele or TT genotype had an increased risk for VaD in general populations (OR, 95%CI: 1.27, 1.01-1.59; 1.41, 1.06-1.88, respectively), and a significant association was found in allele contrast, recessive, and dominant model in Asian populations, but not in Caucasian populations.
CONCLUSION: The MTHFR C677T polymorphism (mainly TT genotype) is associated with developing VaD in general populations or Asian populations.

2010
Zhang MY1, Miao L, Li YS, Hu GY. Meta-analysis of the methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to Alzheimer’s disease. Neurosci Res. 2010 Oct;68(2):142-50. doi: 10.1016/j.neures.2010.06.011. Epub 2010 Jun 30.

No clear consensus has been reached at the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and Alzheimer’s disease (AD) risk. Thus in this meta-analysis, a total of 19 case-control studies was assessed to evaluate the possible association. The data demonstrated that the frequency of T677 allele (T vs. C) was significantly associated with susceptibility to AD in all subjects (OR=1.15, 95% CI=1.06-1.26) and in East Asians (OR=1.22, 95% CI=1.08-1.39). … A subgroup analysis in the subjects without APOE epsilon4 alleles showed T677 allele significantly increased risk of AD in all subjects (OR=1.21, 95% CI: 1.04-1.42) and in East Asians (OR=1.28, 95% CI: 1.06-1.55). However, no association was found in Caucasians. In conclusion, this meta-analysis supports that MTHFR C677T polymorphism is capable of causing AD susceptibility in East Asians, not in Caucasians.

2011
Hua Y1, Zhao H, Kong Y, Ye M. Association between the MTHFR gene and Alzheimer’s disease: a meta-analysis. Int J Neurosci. 2011 Aug;121(8):462-71. doi: 10.3109/00207454.2011.578778. Epub 2011 Jun 10.

RESULTS: This meta-analysis demonstrated that the MTHFR T allele or dominant model for T allele (CT + TT) had an increased risk for AD in combined populations (OR, 95% CI: 1.13, 1.05-1.21; 1.18, 1.07-1.31, respectively), and a significant association was found in allele contrast, recessive, and dominant model in Asian populations, but not in Caucasian populations.
CONCLUSION: The MTHFR C677T polymorphism is associated with AD in Asian populations, but not in Caucasians.

2013
Dwyer R, Skrobot OA, Dwyer J, Munafo M, Kehoe PG. Using Alzgene-like approaches to investigate susceptibility genes for vascular cognitive impairment. J Alzheimers Dis. 2013 Jan 1;34(1):145-54. doi: 10.3233/JAD-121069.

Vascular cognitive impairment (VCI), including vascular dementia, is the second most common dementia after Alzheimer’s disease. Despite its prevalence, the genetic etiology of sporadic VCI is largely unknown. … Associations of increased risk for VCI were found for APOE ε4 (1.818 (95% CI = 1.611-2.053), p < 0.001; n = 3,554 cases, n = 12,277 controls) and MTHFR rs1801133 (1.323 (95% CI = 1.061-1.650) p = 0.013); n = 659 cases, n = 981 controls). There was marginal evidence of a protective effect for APOE ε2 (0.885 (95% CI = 0.783-0.999), p = 0.048; n = 3,320 cases, n = 10,786 controls). This systematic study of all published genetic association studies of sporadic VCI supports MTHFR and APOE as susceptibility genes for VCI.

2013
Grarup N, Sulem P, Sandholt CH, Thorleifsson G, Ahluwalia TS, Steinthorsdottir V, Bjarnason H, Gudbjartsson DF, Magnusson OT, Sparsø T, Albrechtsen A, Kong A, Masson G, Tian G, Cao H, Nie C, Kristiansen K, Husemoen LL, Thuesen B, Li Y, Nielsen R, Linneberg A, Olafsson I, Eyjolfsson GI, Jørgensen T, Wang J, Hansen T, Thorsteinsdottir U, Stefánsson K, Pedersen O. Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets. PLoS Genet. 2013 Jun;9(6):e1003530. doi: 10.1371/journal.pgen.1003530. Epub 2013 Jun 6.

Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B(12) (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B(12) and folate measurements, respectively. We found six novel loci associating with serum B(12) (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B(12) and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer’s disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B(12) or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations.

OTHER RECENT STUDIES

2013
Mansouri L1, Fekih-Mrissa N, Klai S, Mansour M, Gritli N, Mrissa R. Association of methylenetetrahydrofolate reductase polymorphisms with susceptibility to Alzheimer’s disease. Clin Neurol Neurosurg. 2013 Sep;115(9):1693-6. doi: 10.1016/j.clineuro.2013.03.015. Epub 2013 May 6.

RESULT: Genetic analyses did not indicate a significant association between the MTHFR C677T mutation and AD (C/T: 63.15% versus 39%, p=0.087). However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p<10(-3)). Our data suggest an association between the MTHFR A1298C mutation and AD; however, the MTHFR C677T mutation did not contribute to susceptibility for AD.
CONCLUSION: The MTHFR A1298C polymorphism is a possible risk factor for Alzheimer's disease.

2013
Farkas M1, Keskitalo S, Smith DE, Bain N, Semmler A, Ineichen B, Smulders Y, Blom H, Kulic L, Linnebank M. Hyperhomocysteinemia in Alzheimer’s disease: the hen and the egg? J Alzheimers Dis. 2013;33(4):1097-104. doi: 10.3233/JAD-2012-121378.

Hyperhomocysteinemia is associated with Alzheimer’s disease (AD). The causality of this association is controversial. … In conclusion, this data may argue that folate reduction and hyperhomocysteinemia may contribute to neurodegeneration and may also be triggered by neurodegenerative processes, i.e., represent both a cause and a consequence of neurodegeneration. Such a vicious cycle may be breakable by dietary or supplementation strategies increasing the availability of 5-MTHF.

2013
Jin P1, Hou S, Ding B, Li D, Liu L, Li H, Li L, Zhao G, Shao Z, Liu X. Association between MTHFR gene polymorphisms, smoking, and the incidence of vascular dementia. Asia Pac J Public Health. 2013 Jul;25(4 Suppl):57S-63S. doi: 10.1177/1010539513492819. Epub 2013 Jul 15.

This study investigated the relationship between N5,N10-methylene tetrahydrofolic acid reductase (MTHFR) polymorphisms, smoking, and vascular dementia (VD). … The T allele frequency was significantly higher in the VD group than in the control group (P < .05). Among patients who smoked, the relative risk of VD in patients with the TT genotype and T allele was higher than in the control group (P < .05). Therefore, the smoking group with the T allele has the highest risk of VD, and synergy appears to exist between the MTHFR gene polymorphisms and smoking in susceptibility to VD.

About Genetic Risk & Celiac Disease

23andMe Celiac Disease Risk Markers

[This was a reply to an email question about genetic risk of celiac. I have so much to share here, but so little time for blogging, that I decided to grab this part, and hope to add more of my recent explorations in the future. Not TOO distant, I hope!]


Like so many people, I failed all the blood tests for celiac, despite having a boatload of symptoms. That was why I took the 23andMe test for celiac markers, with the results showing 4.07 times the normal risk of celiac. In the general population, risk is 0.24%; mine was 0.96%. There are currently 4 known genetic markers for celiac:

* HLA-DQA1 (SNP rs2187668)
* 4q27 (SNP rs6822844)
* 3p21 (SNP rs6441961)
* 3q28 (SNP rs9851967)

I have 3 of the 4, all except the last and least important one, which is what made for 0.96%. Now, ~1% that sounds awfully small, but the genetic risk combines with a variety of other risk factors.

“Estimates of the heritability of Celiac Disease vary. Risk factors other than the SNPs mentioned here include having European ancestry, family history of Celiac Disease, and a personal history of other autoimmune disorders. These disorders include Systemic Lupus Erythematosus, Type 1 Diabetes, Autoimmune Thyroid Disease, and Rheumatoid Arthritis.”

I have European ancestry, family history, and a family history (not personal history) of the autoimmune disorders listed as examples, with a personal history of autoimmune disorders not listed as examples. My diagnosis came from combining all of these:

* genetic risk factor PLUS
* family history PLUS
* ancestry PLUS
* other autoimmune disorders PLUS
* symptoms PLUS
* blinded trial

You see, the inclination of the docs was to read the symptoms as meaning a combination of a bunch of other possible conditions, which they’ve been attempting to treat for 10-20 years. Unsuccessfully. But we kept trying. Believe it or not, this made sense, specifically because, until we had all that information, the risk of the other conditions was higher than the risk of celiac, making it much more logical to explore those options.

They were reluctant to consider celiac, in part because it is a “fad” currently prone to self-diagnosis. Docs rightly tend to mistrust self-diagnoses of current fads, but then every now and then the fad was right! LOL! The other reason they were mistrusting this “self-diagnosis” was because I had atypical presentation of the symptoms. Most folk have primarily gut problems. I had mostly skin. Most folk with celiac related skin problems have those show up on limbs and back. Mine were worst on my face. Medically, it didn’t LOOK like celiac or dermatitis herpetiformis. They weren’t sure what it was, but it didn’t look like what it turned out to be. So you really can’t blame the docs.

But when you combined all these risk factors, you ended up with roughly 1/4 risk instead of 1/100. Big difference. Then the blinded trial tipped the balance. When you have someone with a 1/4 risk of celiac and symptoms and they pass a blinded trial, well, the reluctance to diagnose celiac faded.

EDIT:

I am adding a link to the article citation which was referenced in the test results. For those who want to explore more deeply.

van Heel DA, Franke L, Hunt KA, Gwilliam R, Zhernakova A, Inouye M, Wapenaar MC, Barnardo MC, Bethel G, Holmes GK, Feighery C, Jewell D, Kelleher D, Kumar P, Travis S, Walters JR, Sanders DS, Howdle P, Swift J, Playford RJ, McLaren WM, Mearin ML, Mulder CJ, McManus R, McGinnis R, Cardon LR, Deloukas P, Wijmenga C.
A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21.
Nat Genet. 2007 Jul;39(7):827-9. Epub 2007 Jun 10.
http://www.ncbi.nlm.nih.gov/pubmed?term=17558408

Lessons from Gaucher Disease and MTHFR Deficiency

Second Life: Relay for Life 2007: Angel in the Cherry Blossoms

A friend of mine was diagnosed with Gaucher’s Disease this week. (Gaucher is pronounced the French way, Go-Shay.) For most folk this would be a bad thing. For her, it was a gift. It reminded me of when I finally got my celiac diagnosis. I’d been sick at varying levels for at least 20 years. Finally having a diagnosis and being able to DO something about it was … unimaginable. Imagine eyes raised to heaven, and angels singing with serene beauty. A sense of humble joy, and relief.

Then, for me, finding the MTHFR aspect, and realizing it isn’t entirely clear where the celiac leaves off and the MTHFR begins, or visa versa. They seem to be pieces in the same puzzle, interacting in ways that are not necessarily straight forward. The MTHFR in particular is complicated, since it has been overlooked and neglected by the healthcare system until very recently, and like celiac in the USA, is often overlooked.

Well, surprise! Gaucher has some real similarities to this scenario. Like MTHFR deficiency, Gaucher disease has a very rare and severe (read: deadly) manifestation, AND a milder version often overlooked or misdiagnosed, but often disabling. Both Gaucher disease and MTHFR deficiency involve a genetic profile that creates a lack of an enzyme needed to break down a chemical in the body. Lack of the enzyme and inability to break down the chemical compound means that the body ends up with too much of something it doesn’t need and doesn’t want, and not enough of something it does need. And, for both these conditions, that imbalance then causes a wealth of confusing symptoms and a poverty of health and ease.

For MTHFR deficiency, the enzyme needed is Methylenetetrahydrofolate reductase (MTHFR). (Duh. Obvious.) MTHFR, when you have the right stuff, converts homocysteine (toxic, as in bad for you) into methionine (essential, as in something your body needs). Too much homocysteine is related to a lot of difference diseases, most commonly heart disease, nervous system and psychological diseases, and osteoporosis and fragile bones. Recently, there is research showing that too much homocysteine might be related to a number of cancers. There’s plenty more, but that gives you the idea that this can be trouble.

For Gaucher disease, the enzyme needed is the lysosomal enzyme glucocerebrosidase. That’s a mouthful, but I bet my friend manages to learn to make it roll off her tongue easily in no time! Just as with MTHFR, not being able to break down the chemical, means you end up with too much in your body, and then that causes damage. For Gaucher, instead of getting too much homocysteine, you have too much in the way of glucocerebrosides. What is supposed to happen with the glucocerebrosides is that they are broken down into the sugar called glucose and a fat called ceramide. Your body knows how to use those. But a person’s body kind of chokes on the glucocerebrosides. The cells that are supposed to break them down (a type of white blood cell called macrophages) actually get bloated and confused, and stop doing what they are supposed to do. In case you don’t already know, white blood cells are part of your immune system, so with the macrophages in trouble, that means EVERYTHING is in trouble, but especially the spleen, lungs, kidneys, and often the brain. Talk about scary! Early signs include anemia, easy bruising, bone pain, and easy fractures. Those early signs of Gaucher are coincidentally also sometimes early signs of celiac disease and MTHFR deficiency, BOTH. See why it is so hard to diagnose these things?

Here’s another similarity, but this one between me and my friend’s diagnoses, rather than the diseases. Both both of us, the symptoms we showed were not the expected presentation. We had the disease, but the docs missed it for years simply because what they were trained to look for was different from how it manifested in our bodies. Let me try to say that a different way. The symptoms for both of these come from the build up of the bad stuff in our bodies, but that build up can cause things to break down in more than one way. For most people, certain things break down, but for both of us the stuff that broke down was unusual. These are the kinds of diagnoses that make perfect sense after the fact. Hindsight is always 20/20, right? For my friend, her family had approximately the same symptoms for five generations, and no one ever figured it out. For me, we are less sure, and less clear, but I see echoes of my symptoms in old family stories. I wish I could go back in time and tell my beloved grandfather to change his diet so that he wouldn’t die crippled and in pain.

So with both of us having a disease that didn’t “behave right”, how did we end up with our diagnoses? You know mine — personal genomics. It took those genome scans to give the right clues, and then to combine those with some educated guesses about treatments. For her? Well, guess what? It was personal genomic again! Well, how do you figure that? What a surprise. Or maybe it is no surprise that both of us have become rabid evangelical supporters of personal genomics, especially for anyone with mysterious ongoing symptoms or chronic diseases that just don’t seem to get genuinely better no matter what you do.

Since my friend’s diagnosis, a bunch of us on Twitter have been reading up on Gaucher. I stumbled on this article today, and it set off a lightbulb in my mind.

Sidransky, Ellen. Gaucher Disease: Insights from a Rare Mendelian Disorder. Discovery Medicine October 27, 2012. http://www.discoverymedicine.com/Ellen-Sidransky/2012/10/27/gaucher-disease-insights-from-a-rare-mendelian-disorder/

Here is the sentence that rang like a gong.

“It has become increasingly clear that “simple” recessive disorders provide unique insight into the complexities of common diseases.”

Deeper into the article there is a second similar sentence.

“These rare inherited disorders often offer a unique window into seemingly unrelated diseases.”

You start talking about “seemingly unrelated diseases” with celiac and you end up with a laundry list of associated conditions that cover the entire body and every major organ system. Ditto for MTHFR deficiency. And a lot of the conditions are the same ones. And they are also associated with Hashimoto’s Disease, chronic fatigue syndrome, myalgic encephalomyelitis, miscarriages, preterm labor, osteoporosis, bipolar, schizophrenia, depression, migraines, epilepsy, memory loss, cognitive decline and mental confusion, and simple things like joint pain, and weird things like hidradenitis suppurativa, and … and … well, I could go on a long time. I started to draw up a list once, to try to organize them all, but it was a bit overwhelming.

This article about Gaucher disease was describing the same sort of far ranging connections to other diseases.

“Studies of patients with Gaucher disease have led to unanticipated research directions impacting several distinct medical disciplines. Some notable examples include the link between mutations in the glucocerebrosidase gene and the development of Parkinson disease and related Lewy body disorders, elucidation of the role of glucocerebrosidase in skin barrier function and neonatal viability, and the connection between lysosomal transport and myoclonic epilepsy.”

Like Ellen Sidransky, I am now asking if there might be a significant pattern forming here. How many of our chronic diseases are actually caused by a cascade of events deriving from a simple bit of biochemistry gone wrong in our bodies? For me, this was easily addressed with a change of diet and new vitamins. For my friend it won’t be quite as easy (enzyme infusions), but it is still a LOT easier than all the meds she’s been taking and hospitalizations she’s been going through. Quality of life improvement is unbelievable, at least for me. Her treatment hasn’t started, but I expect the same phenomenal improvement in quality of life (QoL).

On the one hand, part of me says, “Why? Why did it have to take so long? Why was it so darned hard to figure out? Was there a point to all these years of struggle and pain?” On the other hand, I kind of ‘get it’, I can see how difficult it must have been to figure out. I still resent all the docs who tried to convince me it was in my head, but I am also so very very grateful that the personal genomics tests have reached the point where they are more accessible, and CAN help people like me. Like my friend. And hopefully, many many more.


A Few Resources

Gaucher Basics: http://www.childrensgaucher.org/about-gaucher/gaucher-basics/

Genome.gov: Learning About Gaucher Disease: http://www.genome.gov/25521505

Science Daily: Macrophages: The ‘Defense’ Cells That Help Throughout the Body: http://www.sciencedaily.com/releases/2010/08/100826141232.htm

NINDS Gaucher Disease Information Page: http://www.ninds.nih.gov/disorders/gauchers/gauchers.htm