Monday, August 14, 2017

The Long Journey to HoFH

Well, it has been a long journey, of about 36 years, to diagnose me with the correct kind of FH. 36 years. I have thought that I have known everything there is to know about this disease, and definitely everything there is to know about my disease. But as so many times before – there is still so much more to find out.

As I have said before, it boggles my mind how misdiagnosed or undiagnosed FH is when it is so easy to test for it. I knew I had FH at the age of 8, which is relatively early, so I have always considered myself one of the lucky ones: I have known to keep an eye on my numbers, on what is new in medicine and on all the other diseases that are triggered by it.

But there was at least one more 'x' in the equation which was not solved till last week: I have, in fact, Homozygous Familial Hypercholesterolemia (or HoFH: https://thefhfoundation.org/about-fh/homozygous-familial-hypercholesterolemia – this link will explain what it is and why it is different than the other type of FH, the Heterozygous kind, or HeFH).

Over the years, there have been guesses. About 50% of my doctors have told me that I might be HoFH, and yet another 50% were sure I was HeFH. The difference in their opinion was usually explained like this: because my levels were very high when unmedicated (730mg/dl when I was a kid, 520-600 mg/dl as a young adult), some doctors were sure I am HoFH. They generally believe that HeFH levels don't usually go above 400mg/dl. For the other group of medics who believed I am HeFH, the reason for their picking that form of FH instead was that I was responding somewhat to medication. Some people believe that HoFH patients don't respond as well, or at all to medication.

Although my cholesterol has yet to be truly “normal” (the LDL was still 150 mg/dl last time we checked) now that I take several medications (http://livingwithfh.blogspot.com/2016/07/my-current-drug-regimen-and-diet.html), it has gotten down a lot over the years. I also have never done apheresis. For this reason, some doctors believed I had the HeFH form of FH.

Why is it important to find out?! Because it can make a difference in your treatment. There are medications that are approved only for HoFH patients that I have never been exposed to, nor talked about to, because there was no clear evidence that is my kind of FH.

I have known for a while that the only positive way to know the kind of FH you have is by ordering a genetic test. This year, I went to a FH Foundation training for their advocates. There, I made a lot of friends (I am speaking about this experience in this entry: http://livingwithfh.blogspot.com/2017/06/when-i-met-my-extended-fh-family-and.html) and some of them had done their genetic test and they were sharing the information about how specific the results are, how they give you the exact gene number that is pathological, what mutation you have, and which protein you're deficient in, etc. One of the leaders of the organization piqued my curiosity when she wondered out loud whether I had He or HoFH, knowing that my cholesterol levels were in the 700s from early childhood and understanding my early history of cardiovascular disease. Hearing her suspect what I had also been wondering about finally broke the medical camel's back and I decided after our training to find out for sure.

The specialist doctors they invited to this training also got into great detail about why not two FH conditions are alike and why it's important to know exactly what condition you have, to address it with the correct treatment. If you have not checked this resource yet and you are looking for more information about your disease and options for treatment , check them out (thefhfoundation.org).  

This test is not, however, as routine as your cholesterol check, as you can imagine. You would have to work with your cardiologist or lipidologist and they usually work with a genetic lab that can perform the test. I looked into it with my own cardiologist (who is also a lipidologist) and he referred me to this genetic lab for the test. So, for my unsatisfied curiosity, and possibly for a more accurate treatment, I researched the options I had for a genetic test with him and the lab.

And, last week I got my result and at the top of the page it's clear as day:

The individual is homozygous for the p.A540T likely pathogenic variant in the LDLR gene.”
Apparently, I got this particular gene from both my parents, as I have 2 identical ones (as I understand it) that are 'sick': p.A540T. The results go into more details about which exon of the gene is affected and which nucleotide position, as well as what other names this mutation is known by. If this all sounds like Greek to you, know that it does to me, too. I am taking baby steps to figure out what it all means, exactly. You can then take all this information to Google and find out more about the research done on your specific mutation.

The process to being here today, with the diagnosis in hand, was a bit lengthy for an impatient human like me, but … I would recommend it to anyone that has access to it, as it can be well worth it for the accuracy of your treatment.

It started, like I said, with me bringing it up to my cardiologist. He was in the HoFH camp, and he agreed that he would be curious to know for sure, too. Doctors don't typically recommend the genetic test, I believe, because this test is mostly not covered by insurances and it is not cheap. So, they don't bring it up with patients because they know people won't most likely pay for it.

The doctor called the genetic testing company, and I got a phone call from them after about a week from my phone call to the doctor, to confirm my address. After about another week, they sent me a package with a couple of things inside:
  • A test tube where my sample of saliva would go
  • Instructions about how to safely obtain a sample
  • A FedEx self-addressed envelope to return the sample to them
  • A form where I specified what gene I want them to test (I wrote in “familial hypercholesterolemia” - I am always sure not many people even in the medical field know or refer to it as “FH”), some other personal information, and my health insurance information.

The test tube used to collect a sample of saliva for the genetic test. 

I sent them the sample with a copy of my insurance card and the form and I got another phone call from them to tell me they have received the package and have called my insurance. They said the insurance will pay for most of it, but there is still a $500 co-pay that I need to pay myself. I had to verbally agree to pay it, or else they would not have gone on with the test. In addition to my health insurance I have an HSA account and I had money in that account that will pay for this. So, the payment portion worked out.

About 3 weeks later (we're about 5 weeks into this whole thing now), I got a voice mail from my doctor: they had received my results and I am HoFH positive, and we shall talk more about this on our next appointment. He left the voice mail on a Friday. I called my nurse the following Monday to ask if I can come by to pick up a copy of my results, as I needed it to research more into this. I was expecting the company who sent me the sample kit to send me a copy of the results, as well, but that was not the case.

This is not a complete DNA analysis by any means: they simply test for the gene you request and that is all. They are not going to do a complete genetic profile with such a test. So I didn't find out interesting things like I might be Russian or something … They just test for this one gene and whether there is any pathology associated with it or not. They also tell you that is not 100% accurate and the doctor warned me about that, also.

I started researching right away this gene mutation that I have to understand what the connection might be between this specific form of FH and the treatment I should be under. So far, I have not been successful to find such a connection, but I have my appointment with my doctor coming up, and I hope that will answer some questions. As I mentioned before, I know that there are drugs that are approved only for HoFH, which I have never been on before. So, when I thought I have tried everything that has ever been invented for this disease, it turns out: I didn't. No idea what kind of door this new finding is opening, but I just know that I will be learning a lot yet, and looking at this life-long disease I thought I knew in and out in a new light.

Through the FH community, I have made contacts with other patients or parents of patients, and they sometimes send me information about various things. One of such parent sent me a link to this website, where you can localize your gene and find out more details about it: http://www.ucl.ac.uk/fh-old/muttab.html .

It is pretty interesting. For instance, my gene is found in the UK, Germanic, or Icelandic ethnicities. I guess this makes some sense, as I knew for sure that I am German on my father's side. I have found other information online about this specific gene, but most of the results are in .pdf format. If you know your pathological gene, just do a Google search for it, and you're bound to find more information (doesn't Google just know it all nowadays?!).

I will have to say that all the information I have found online so far is not very easy to consume. I have found a number of medical treatises that are very scientific and very dense. Not your regular brochure you pick up at the doctor's office. I almost flunk genetics in high school, so I don't converse very easily in genetic-ese, but I am trying to absorb as much information as I can from what I can find online to at least understand how genes work and to formulate some questions for my doctor. I will come back with more of what I learn from my doctor, too, and update here.

Some things did make sense, in my short research so far: I know now that each of our parents have 2 sets of genes. They pass onto us one from each of their sets, and we end up with two genes of our own (one from each one of them). I knew for absolute sure that my father had FH, and I have suspected all my life that my mom had it, too, although she argues about that (she just says her cholesterol is bad because of what she eats, but … I don't think so). My mom's parents divorced when she was 3 and her dad died shortly after that. She had no relationship with her dad's family, so we don't know anything about that side of her genes. Her mom's cholesterol was always normal.

Now, I could positively tell her that she indeed has FH, too, like I suspected, just from my test. My mom is probably HeFH, too, also based on her numbers. So, it turns out, mom had one good gene and one bad, dad had one good gene and the same one as my mom's bad (my parents are not related in any way, that we know of!), and they each passed on the two bad ones to me. My sister has just been officially diagnosed with FH, too, as well as her youngest son who is 6. Their levels are in the HeFH range, so she probably got a bad gene and a good one from our parents, but she is also submitting for genetic testing as well, to find out for sure what form of FH she has. We always say that if you find a patient with this disease, you have found a family – and that is so true!

No matter what you find out: if you can afford it, I would advise everyone to get this test done, just to ensure that your specialists will have the full picture and they will know what exact tool from their arsenal to work with for your case alone. I have seen so many different treatments in all the patients that I have met that there is no “one med fits all” when it comes to FH. So, the more information you have about your specific type, I think the faster you are on the way to finding what works for your body alone.

There are a couple of sheets in the package that came with my result to help you understand FH in general – those were things I knew, overall. There is also a list of recommended resources and the list is:


Good health, you all, and never stop searching for answers!


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