ApoE4 in patients with Marfan Syndrome?

[cstormer]

Hello all! I'm new to the forums and recently discovered I am a carrier last year.

Some back story about how I ended up here and what prompted my question (no pun intended): I'm 21 years old, and have been dealing with scoliosis for the past few years (40 degree curve). I visited multiple orthopedic specialists who all told me I would need surgery. One surgeon in particular expressed serious concern about the possibility of Marfans Syndrome due to my physical characteristics; I am tall and lanky, 6'6, 140 lbs, as well as having flat feet and poor eye sight. From there I delved into multiple tests to further investigate.

The tests all went well. However, the Marfans doctor said the possibility was in the air "I can't tell you that you have it, and I can't tell you that you don't". During an echo-cardiograph the assistant recommended a scoliosis specialist in the area who focuses on remedying scoliosis through non-evasive techniques, the use of specialized exercises and nylon/velcro strap braces.

I started seeing this doctor who was optimistic that he could eventually get my back to under 30 degrees. I also tested for osteoporosis, although it is uncommon at my age, I decided to due to family history and found I have -2.5 bone density. In order to fix my back, I had to first get my bone density under control; other wise my back would continue to get worse. We did a comprehensive test of everything you could think of (vitamin D, free testosterone, total testosterone).

This is when I found out about my Apoe4 alleles. I completely flipped my lifestyle, changing my diet to ketogenic, taking lots of vitamins, working to build some muscle/fat, and wearing my back brace every day. I found it counter intuitive to be on a low carb diet while trying to gain fat / muscle. If anyone has advice or tips on any of this please feel free to share!

LONG STORY SHORT: I'm curious to know if there has been any research regarding the presence of ApoE4 alleles in patients with Marfan Syndrome (or osteoporosis for that matter) considering the parallel problems in cardiovascular health.

P.S Here is a link to the scoliosis treatment for those that are interesting in case it may help any https://www.treatingscoliosis.com/

[ccfield]

Welcome Cstormer!

I'm very impressed with your perseverance! I was not quite so steadfast in the face of obstacles at your age. It's also very encouraging that you have found a specialist that is going the route of non-invasive correction and that he ran such comprehensive tests. It sounds like you are in good hands my friend.

The fact that you have started the prevention lifestyle at your age is phenomenal. Reading your post inspired me because you are definitely taking care of business! Kudos to you Cstormer.

I empathize with your dilemma of Keto diet vs. muscle/fat gain. I am also on the Keto diet (modified) and because I exercise rather vigorously a few days a week, I have played around with pushing my protein intake as far as possible and still stay in mild ketosis (@1.5mMol is my happy place), especially on days when I'm pushing hard.

A few notes about the site:
If you have not yet done so, I highly recommend that you read the Primer. It is written by physician member Stavia and is full of great information on all things ApoE4. You've probably also already noted the 'Search' feature at the top of the page. It will guide you to previous posts on specific topics.

Know that we are thrilled you are here. The wealth of knowledge among ApoE4.info members is astounding and I'm certain they will chime in with their thoughts on your question. I rest assured knowing that many of the members are more well-versed than I in regard to your question and will most definitely have thoughts to share with you. If you have any questions, please don't hesitate!

- Carrie B

[slacker]

Hi Cstormer;

At your height and weight, you probably need to eat just about anything to gain weight! I personally have lost weight that I didn't need to lose attempting a ketosis diet, which is common in the low weight/underweight clan. Low body weight alone is a risk factor for osteoporosis. Hopefully your specialist also checked for hyperparathyroidism and celiac disease as possible drivers of osteoporosis.

Protein intake is a hotly debated topic on our site. You can search for prior discussions on protein by clicking on the magnifying glass in the toolbar right upper corner. Narrow the search by selecting "Topic titles only."

[cstormer]

Hi Cstormer;

I personally have lost weight that I didn't need to lose attempting a ketosis diet

Thanks for the great insight, slacker!

Luckily, I haven't seen any weight loss thus far. I'm actually enjoying the low carb diet, I've never been a poor eater, but I think I speak for everyone when I say that I miss bread I've always been skinny with a large appetite and find it hard to feel full with the low carb diet, so I typically eat multiple helpings. I've been wondering if I should try out the Mediterranean diet? I do have increased levels of homocysteine which can occur with hypothyroidism, so that's probably something to look into.

Thanks!
Cstormer

[cstormer]

Carrie,

Thanks for the warm welcome and awesome feedback! I've only scratched the surface of the primer...there's a lot of great info there, the wealth of knowledge among the users is really impressive. Its good to hear feedback about balancing diet, I definitely need to get a keytone meter to monitor my levels and dial in my diet.

Best,
Cstormer

[slacker]

I've always been skinny with a large appetite and find it hard to feel full with the low carb diet, so I typically eat multiple helpings. I've been wondering if I should try out the Mediterranean diet? I do have increased levels of homocysteine which can occur with hypothyroidism, so that's probably something to look into.

Many people feel full all the time when in ketosis. Maybe you aren't getting enough fat?

Stavia has good information on eating a healthy diet and homocysteine in her Primer. An easy way to find these sections is to open the Primer, then use the "search this topic" function on the left under the Primer's title. Happy trails!

[circular]

However, the Marfans doctor said the possibility was in the air "I can't tell you that you have it, and I can't tell you that you don't"...

LONG STORY SHORT: I'm curious to know if there has been any research regarding the presence of ApoE4 alleles in patients with Marfan Syndrome (or osteoporosis for that matter) considering the parallel problems in cardiovascular health.

Hi cstormer!

Welcome. Glad you found us and are taking charge of your health at an early age.

A number of us here have connective tissue disorders, although I've not been aware of Marfan's being mentioned yet. May I ask what kind of doctor evaluated you for Marfan's? Were they only a Marfan's specialist or also a connective tissue disorder specialist? Most likely a Marfan's specialist would be more knowledgeable about other connective tissue disorders than the average doctor, and maybe you've abbreviated the upshot for us, but 'you may or may not have Marfan's' seems like a rather oversimplified response to your situation, especially given the surgeon's concerns.

I'm no expert, but I do have a connective tissue disorder. There are many different genes that feed into one's connective tissue makeup, leading to many different kinds of connective tissue disorders, Marfan's being just one. Some genes determine specific connective tissue disorders, while for other connective tissue disorders the genetics are less clear. In any case there are often crossovers between types of connective tissue disorder and spectrums of clinical manifestation. This is why I wonder if you saw a true connective tissue disorder specialist. Even if you don't have Marfan's you may well have a connective tissue disorder, which is essential to know if you ever do need to contemplate surgery again. I have one of the subcategories of Ehlers-Danlos, but I also have subtle Marfan's traits and was told that it wasn't clear whether those traits were Marfan's 'penetrance'. It is clear that I have connective tissue concerns.

I'm not aware of any studies done looking together at apoe and connective tissue disorders. Despite the medical street talk that connective tissue disorders are 'rare', it's obvious to me that at least the 'generic' hypermobility form of Ehlers-Danlos is quite common. So we do see this one in our apoe4 community. There appears to be a strong inflammatory component with EDS-hypermobility, and apoe4 also has an inflammatory component. This may be making life a bit more difficult for some who are dealing with both situations. I'm not sure whether Marfan's has inflammatory overlap in and of itself.

I also think the cardiovascular vulnerabilities are broadly different between apoe4 and the connective tissue disorders that are associated with cardiovascular complications. With apoe4 it's more of a lipid management issue while with some connective tissue disorders the problem is with poor integrity of the arterial walls that are weak and can burst (but not always and not typically at your age!). That being said, there would probably be interaction between these cardiovascular pathologies increasing overall susceptibility to CVD.

Just consider these some thoughts to address with a qualified medical professional This page hints at the complexity here. If your first doctor wasn't a connective tissue geneticist and didn't test for these genes, you might want to seek another opinion with a specialist like that.

[cstormer]

May I ask what kind of doctor evaluated you for Marfan's? Were they only a Marfan's specialist or also a connective tissue disorder specialist?

He was specifically a Marfan's specialist. I also found it strange that he could come to a conclusion as basic and uninformative as that. I tried to push for further answers or methods but he said that the technology hadn't caught up yet which I knew was not the case.

I will definitely need to continue to investigate this as it's apparent that link between connective tissue disorders and ApoE4 may not be a coincidence.

Thanks for all of the great info!

[Julie G]

Hi cstormer! We've got (more than coincidence?) a surprising number of folks here with connective tissue disorders. I'm among them with EDS. My little brother experienced an aortic perforation before age 30 that looked like Marfan Syndrome although he didn't clinically meet the other diagnostic criteria. He's not exceptionally tall; only around 6 feet. Another brother experienced a carotid dissection, also very young- early 30s. (They both survived!) Their combined experiences (plus our symptoms) pushed my son and I to get tested for vascular EDS. We were negative, but were instead dxed with classic EDS, which can also be susceptible to vascular complications. Given the Marfan suspicion, have you had an ultrasound of your heart... just to be safe?

IF there is a connection to E4, my guess is that it may be meditated via a reduction of collagen leading to a lack of integrity in many of our connective tissues. As you know, connective tissue disorders are characterized by a collagen defect/deficiency. I've found several papers that have found E4 mice have reduced levels of Type 4 collagen that leads to increased blood brain barrier permeability. Here's one of those papers along with a graph showing the collagen deficiency in 3/4 and 4/4 genotypes. I can't help but wonder if this reduction in collagen (in a dose dependent fashion) could contribute to the higher than expected number of E4 carriers with connective tissue disorders? When I have more time, this is a rabbit hole, I want to more fully explore.

gr4.jpg

[circular]

Julie you're my alter ego. Every time I try to rationalize something not being the case you present data to make me question The cup of coffee at my side is dedicated to you!