Douglas Lowell, Find A Cure Panel.
Today, I welcome Cynthia Villwock, HoFH caregiver and advocate.
Cynthia Villwock, HoFH caregiver and advocate
Thank you for asking me
Douglas Lowell, Find A Cure Panel.
Cynthia, I want to start by defining Homozygous Familial Hypercholesterolemia (HoFH) hereafter HoFH. What is this disease as most people have never heard of it?
Cynthia Villwock, HoFH caregiver and advocate
In layman’s terms it means that an individual received two broken copies of the gene that takes in cholesterol and breaks it down. Without a working copy there is no way for the body to break down LDL cholesterol (the bad cholesterol) and it reaches high levels in the body. About 1 in 230,000 individuals are born with it every year. It is found worldwide irrespective of the country or nationality.
At high LDL levels, and without very aggressive treatment, it is not uncommon for individuals with this disorder to die within the second or third decade of life.
High cholesterol this severe results in “clogging” of the arteries in childhood or early adult life.
Douglas Lowell, Find A Cure Panel.
That is well articulated. Thank you, Cynthia. There are other variants of FH like HEFH. Heterozygous Familial Hypercholesterolemia . How is HEFH defined and how does it differ from HOFH?
Cynthia Villwock, HoFH caregiver and advocate
HeFH means an individual inherited one working copy of the gene and one broken copy. One from each parent. Since individuals with one working copy are able to “somewhat” remove LDL their cholesterol is lower than those with HoFH but still markedly higher than those without any broken genes. This genetic version of high cholesterol is present from birth and actually before birth! This means their high LDL has been wrecking havoc for their entire lives. And it also means these individuals are at higher risk of heart disease than others in the general population who have the “ordinary” or lifestyle caused high cholesterol. Those with lifestyle caused high cholesterol have only had high LDL later in life (adulthood usually and not childhood). So, those with the genetic disorder are at MUCH higher risk of heart disease. In fact, a man with HeFH has a 50% chance of having a heart attack by his 50th birthday and a woman with HeFH has a 30% chance of having a heart attack by her 60th birthday.
Those with HeFH do have one working copy of the gene which means if we can upregulate or produce more of it, we can lower the LDL. This is how statins work. They make it so the individual produces more receptors (the tool used to take in cholesterol and break it down) and if that individual has one working gene they are able to produce more receptors to take in that cholesterol and break it down. Unfortunately those with HoFH don’t have any working receptors so making more of them does nothing to lower their LDL.
Douglas Lowell, Find A Cure Panel.
This is very informative.
Let’s talk about the genetics. So people are born with HoFH. Does this mean that one or both parents have it? What percentage of kids in a given family will get it? How does that work?
Cynthia Villwock, HoFH caregiver and advocate
Now that is an interesting topic! Those folks with HeFH have one working gene and one broken gene. When that individual has a child, they can give that child either the broken gene or the working gene. Everyone inherits one gene from each parent. So an individual with HeFH inherited one working gene from one parent and one broken gene from the other parent. Now, in the case of HoFH, that unlucky child inherited a broken gene from BOTH parents! Each parent must have at least one broken gene in order for a child to have HoFH. And that child must have inherited the broken gene from each parent. Parents who are HeFH have one broken and working gene. This also means they could have each given the working gene to their child. In fact, if two individuals with HeFH have children, statistically they have a 25% chance of having a child with HoFH, a 25% chance of having a completely normal child and a 50% chance of having a child with HeFH.
However, statistics are for the population at large. I know a family with four children, three of which have HoFH!
Douglas Lowell, Find A Cure Panel.
So you have HeFH ? And your parents had what?! And what do your kids have?
Cynthia Villwock, HoFH caregiver and advocate
Yes, I have HeFH. Both my parents also had HeFH. My sister is HoFH.
My husband also has HeFH. Since both myself and my husband are HeFH our children had the statistical chances I shared before. Our daughter is completely healthy and our son has HoFH
Douglas Lowell, Find A Cure Panel.
All noted. Now, you didn’t know your husband had HeFH? It was just a coincidence?
Cynthia Villwock, HoFH caregiver and advocate
We both knew we had high cholesterol and we both knew it was genetic. But meeting and falling in love with my husband was completely by chance!
Douglas Lowell, Find A Cure Panel.
How old was your son when you learned he had HoFH? At birth?
Cynthia Villwock, HoFH caregiver and advocate
We didn’t have a name for it then, but honestly I don’t think it would have mattered even if we did have a name for it. We already knew it was genetic and it caused high cholesterol
We discovered our son had HoFH when he was 7.
He had formed little yellow bumps on his elbows and knees at the age of 5. By the age of 7 when they had grown larger, we took him to find out what they were.
Douglas Lowell, Find A Cure Panel.
There’s genetic testing for HoFH now?
Cynthia Villwock, HoFH caregiver and advocate
They turned out to be cholesterol deposits under the skin caused by his very high LDL
Yes there is genetic testing. I don’t personally recommend it though. The treatment is the same regardless. And, genetic testing can have negative consequences for the ability to purchase life, long term care, and disability insurance.
I actually went to our long term care insurance that my husband and I have and asked what effect a positive genetic test would have had on our ability to purchase our long term care insurance. I was told we would have been denied our insurance. When I inquired why, she told me that our genetic makeup is not modifiable but that just plain ol’ high cholesterol was treatable. They were making a distinction. Not far and not reasonable but discrimination does happen. and GINA the genetic information nondiscrimination act does NOT protect against discrimination for life, long term care and disability insurance.
Our son chose not to have genetic testing. Although he did have it done under a clinical trial and as such it is not in his medical record.
Douglas Lowell, Find A Cure Panel.
That needs to change. What lobbying is being done to address that issue?
Cynthia Villwock, HoFH caregiver and advocate
To be honest, not many folks are even thinking of the negative consequences. Even most who receive genetic counseling are not being told. It seems to be flying under the radar.
Douglas Lowell, Find A Cure Panel.
Let’s talk treatment. Take us through the treatments currently available for HoFH, Cynthia. And how have those treatment evolved over the years?
Cynthia Villwock, HoFH caregiver and advocate
For FH. this is troubling because if treated appropriately, the risks are eliminated. If the LDL can be lowered to adequate levels our risk of heart disease even in HoFH can be greatly reduced or even eliminated.
Oh my, treatments have come a LOOooooooong way!
When our son was first diagnosed in 1999 the only treatments availalble were statins, of which zocor was the only one approved for children, and niacin. Then there was apheresis but it was not widely available at the time since it had just been FDA approved and most hospitals did not yet have equipment. Even now, some people with HoFH must travel 4 hours or more one way for treatment.
Shortly after that Ezetimibe was approved, and then Welchol. Oh, I guess I should also mention that Questran was also available in 1999. I forgot about that one. At any rate, ezetimibe was approved followed by Welchol. It was a number of years later when Mipomersin was approved. My son tried mipo but it had no effect for him. Many individuals did have a good response to it though. Mipomersin was followed by Juxtapid, and then the PCSK9 inhibitors Praluent and Repatha. Finally, Evkeeza was developed.
I should mention that most individuals with HoFH don’t have much response to statins, or PCSK9 inhibitors because they work by increasing the number of receptors and for those with HoFH they don’t have any working receptors anyway so making more of them just …..doesn’t……work.
In our son’s case, he has some partial function on one of his broken genes. Genes can be partially broke! The function is very very small but it does allow him to have a very small reduction in LDL with statins and PCSK9 inhibitors.
The difference for those with HoFH is literally life versus death. When our son was diagnosed at the age of 7 we were told he most likely would not survive to 20. now the prognosis is much more encouraging!
Douglas Lowell, Find A Cure Panel.
Now if someone takes the most effective meds, to what range can their cholesterol be controlled? Does it get into normal range? How has the chances of heart attack been reduced?
I know several HoFH people have had heart transplants.
Cynthia Villwock, HoFH caregiver and advocate
That is a loaded question and has a lot of variables to it. As I mentioned before genes can be completely broken or partially broken. And even with those individuals who have completely nonfunctional genes the response to these medications varies. But in general there will be a reduction with Zetia of 5-10% (or none depending on the person), statins can range from 0-25%, PCSK9 inhibitors can be from 0-30%. But it is MUCH more encouraging for Juxtapid which can lower LDL by 50% even in those who do not have working receptors. And Evkeeza also lowers LDL by ANOTHER 50% which means LDL could be reduced to 25% of the original level with just these two medications! Throw apheresis into the mix and the reduction is about another 50% (much more complicated than this because of the rebound effect with apheresis)
That said, variation is large. For our son’s case, his current LDL is in a great range at 68 the last time it was tested. (he is not on apheresis) But I also have power of attorney for a little guy who is 8 and his response has been less. On ALL of these medications his LDL still sits at 200-250. (he is not on apheresis at this time) So as you can see, it varies from individual to individual
But even the 250 range is wonderful for a child whose LDL started at near 800! Medications have lowered his LDL so that he is more like someone with HeFH….and the consequences of this means he is not expected to have cardiac events until well into adulthood.
Now talking about the consequences of treatment on life expectancy. For our son, since his LDL is now 68 and his calcium score is zero, he is expected to have a “normal” life expectancy! And this is for the kid we were told would not see his 20th birthday! If the LDL can be lowered to adequate levels the risk from FH disappears or is vastly reduced.
Douglas Lowell, Find A Cure Panel.
That’s a blessing, Cynthia.
In addition to be a caregiver, you’re an advocate. How did you get involved in that? As you alluded to below, you have a young charge with HoFH. How did that relationship come about?
Cynthia Villwock, HoFH caregiver and advocate
The same is true for those with HeFH. IF they are treated and treated to the point where their LDL is well below 70, their risk of heart disease is removed. This is why treatment is so imperative for those with HeFH. Remember an untreated manwith HeFH has a 50% chance of having a heart attack by the age of 50,but treated to below 70 and that risk disappears.
I became an advocate with the FH foundation after my father had a 5 way bypass and valve replacement. We (my father and I) went to five different cardiologists/surgeons to determine who we wanted to do his surgery. Of the five only ONE looked at me and asked if I had ever had my cholesterol tested. Clearly the other four were not even considering that I had a 50% chance of inheriting his faulty gene. They missed the chance to save a life. After that experience, I contacted the FH foundation and asked if this was really the norm in America. I was told 90% of those with FH are not diagnosed and not treated. This was enough to catapult me into action.
My relationship with our little 8 year old started 4 years ago, when a father posted on the FH foundation page that his 4 year old had just been diagnosed with HoFH and they were told to “take him home and love him as long as he lives” They were Pakistani and there were very limited treatments in Pakistan. This little four year old would have died. There was no way his LDL would ever be reduced to an adequate level in Pakistn. The father asked if it was really true that there was no hope. I private messaged him telling him about my son and how he WAS able to lead a normal life with a normal life expectancy. We then tried to get some of the medications into Pakistan but we met a brick wall. (you can see our story on our go fund me page). When that failed, we began to work on getting him to America. It took two years, but in July of 2021 they arrived. He is doing AMAZING! Extremely bright, cheerful little boy who has seen his LDL drop from 800 to 200-250.
I just couldn’t turn away. I invited them into our home. What else could we do?
Douglas Lowell, Find A Cure Panel.
That’s a wonderful thing you’re doing, Cynthia. Can you share the link to your GFM page?
Does this child now live with you? Or has returned to Pakistan?
Cynthia Villwock, HoFH caregiver and advocate
https://www.gofundme.com/f/nmqzw-hope-for-ahsan
Actually, we have been helping the entire family immigrate to America. They live on our property but not in our home! 😉
When they arrived I saw that their younger child also had disabilities. He had just turned three but only spoke 6 works in his native language and had just learned to walk 3 months prior. Since then we have been getting this younger child the help he needs as well.
Douglas Lowell, Find A Cure Panel.
That clearly is whole another story but what type of visa did you have to get for them? Did you have politicians helping you? How did you execute that?!
Cynthia Villwock, HoFH caregiver and advocate
The initially came on a B2 visa because we were hoping we could just try out the medications and they could take them back to Pakistan with them. Their visitors visa was valid for 6 months and during that time we started the little guy on all the medications (one at a time to see which ones had an effect on him) It was clear after a few months that there was no way we could send what he needed back to Pakistan. It was then that they applied for an extension to their visitors visa while we tried to sort it all out. Eventually 11 months after arriving they applied for permanent immigration. After applying they had to wait another 6 months before they could be given a work permit. So a year and a half without any means of support. This is why we started the go fund me page . The father has been working the last 6 months. He was fortunate to be able to find a job in his field in only one week after being granted his work permit.
We did ask our politicians to help but were told they could do nothing to help us.
We are still waiting for their “turn” when they will be interviewed and our government will decide if they can stay. We have no idea when their turn will come. We have been told it could be anytime or it could take ten years! We just have no idea.
The father has asked if they must return to Pakistan if my husband and I would adopt their child with HoFH so that he can live…….still makes me cry when I write this. What parent has to choose between their child dying or giving them away?
Douglas Lowell, Find A Cure Panel.
That is a beautiful thing you are doing, Cynthia. Makes my day to hear this story.
