11 Years With a Life Changing Diagnosis

Eleven years ago we were entering Brenner’s Children’s Hospital in North Carolina to try something relatively new. While Andy was not the first patient in the United States to try it, he was definitely in the inaugural class (we think one of the first 5 at least). For 17 months we had given him insulin shots and hooked him up to an insulin pump to keep him alive. We were prepared to spend a lifetime of checks by blood sugars 8-10 times a day, changing out insulin pumps every 3 days and counting carbs for every single morsel of food that went into his mouth.

When we were admitted to the hospital on that night so long ago, we had no idea what to expect. Our doctor was “cautiously optimistic” that this new treatment would work. But even knowing that it might “work”, we knew we were paving an entirely new path in the medical world. Diabetics, especially those with Type 1 didn’t just come off of insulin. We were, as my husband puts it, a freak show on the diabetic floor. While other patients were being admitted in DKA and being treated with insulin, we were starting with a pill in the hopes of stopping insulin. Being a teaching hospital, we were a virtual merry-go-round of student doctor groups. We recounted our story from the last two years of our life, confirming that there was no family history of this on either side. No, I didn’t have gestational diabetes. Yes, he was exclusively breastfed before the initial diagnosis. And on and on for an entire week.

In the hospital with Aunt Alicia

Now we probably check Andy’s blood sugar once every few months. His last A1c was 4.7% which translates to an average blood sugar (in US terms) of about 88 which is right in the middle of normal. He takes 67.5-70mg of glyburide a day, which is roughly 3.5 times the recommended maximum dose of an adult with Type 2 Diabetes.

We don’t know everything there is to know yet. We still deal with all of the co-morbid symptoms like developmental delays and seizures. Some of those issues have gotten better with time, therapy, and an ocean of patience (at which I’m admittedly not always very good). But if being a pioneer and paving the way for new families (and even his own sister) is our purpose, then we have gladly taken on that role. We will continue to search for new treatments that might make his life easier and help him to be a more functional person. He is such a happy person and is growing into a strong young man. I can’t wait to see what the next phase in his life will bring.

Andy this past Christmas with Santa

Closing the Gap: The First Two Weeks on Carbamazepine

We are now at the end of the second week on Andy’s new medicine, Carbamazepine (Tegratol), and so far, we have had no adverse side effects.  We started him on a small dose of 2.5 ml (50 mg) twice per day for the first week and then increased it up to 5 ml (100 mg) twice per day for the second week.  We will continue to increase up to 10 ml (200 mg) twice per day and then get some blood work done to see how he is doing.

No Adverse Side Effects

Our doctor prepared us for the worst by telling us all of the bad reactions to look for; bad rash, grand mal seizures, and discolored urine, etc. We even received a prescription for ??? to have on hand in case of a seizure lasting longer than 5 minutes. That was the one side effect, out of all of them, that scared me the worst. Just thinking about what I would have to do if that happened, insert a medicine in a place I DO NOT want to see on my 12 year old son, sent me into near panic attacks the days leading up to Day 1.

Not only did I have a prescription in case of emergency, I armed myself with support too. As the kids were off school on that Friday and Monday (Easter Holiday), Dan and I both opted to take a day off work and asked one of our babysitters to come as backup. That Friday, as nervous as I was, we tried to make the day as normal as possible for the kids. We played with the kids, building Lego houses and watching videos. Then because Andy wanted stars, we took a trip to the store. We went to Walmart for his favorite foam stars, then Good Will for some much needed shorts, and an Easter dress for Katie. All the while, I was watching him like a hawk and looking for any sign of a new twitch or an unexpected behavior. Thankfully, it never happened.

Improvements Already?

The rest of the weekend and into the next week, Dan and I watched and waited. We were rewarded, not only with no negative events, but, dare I say, improved behaviors? I know it is way to early to tell, but we almost immediately saw Andy be more calm and less aggressive. He even started talking more and his words were more understandable. At least, that’s what we think we have seen.

The hardest part of hope as a parent, is to have an unbiased opinion. In order to make sure we were getting the most accurate data, Andy underwent some baseline testing on the Thursday morning prior to starting the medicine. We will do some follow up testing in 3-6 months. In addition, only his school director knows he is on the medicine, but we are not telling his teachers yet. That way, we can get some unbiased data from them, similar to a “blind study” in the research arena.

Some of the other areas of improvement I’ve personally seen is cooperation with nighttime routines (taking medicine, brushing teeth, going to bed), cooperation with checking blood sugars, calmer behavior in the afternoons, and even less aggression toward me like pinching and hitting. I did see a little increase in the aggression a couple of days this week, but I was also down with the flu. Sometimes, when mom is down, the kids will try to get away with what they can. But isn’t that just a typical childhood behavior in general? LOL

Affect on Blood Sugar

One side effect we did experience, but were really expecting, was a decrease in blood sugars. The question of, if this medicine is closing the potassium channels in the brain, will it, by default, also close potassium channels in the pancreas, was answered pretty quickly. We checked his blood sugars before every meal, when he got home from school, and any other time he seemed to be acting low just in case. The lowest we have seen so far was a 54. That one happened on the first weekend on Sunday night. We were at the end of a long day, from church in the morning, to lunch and and Easter Egg hunt with the neighbors, to playing outside most of the afternoon. It was after 8:00 when I finally started preparing dinner and Andy started rummaging in the kitchen and trying to grab food from the cabinets, the fridge and even right out from my hands. He kept saying he was hungry and needed to eat dinner. Finally I stopped and realized what must be happening and checked him. He was at 54 so I quickly threw together a sandwich and some grapes so he could eat.

Since then, we have seen a couple of 60’s and 70’s, so we lowered his dose of glyburide by a pill in the morning and in the evening. He has stabilized for now, but we will continue to keep a close eye on that until we are sure he is in a better range. I guess the advantage to him being so stable for the last several years is that he is fully hypo-aware and can tell us he needs to eat when he starts to feel it. That was something we never experienced when he was a baby and on insulin.

Going Forward

We still have two more weeks of increasing and waiting to see if there are any issues. There is still a small possibility that seizures can occur, so we are not out of the woods yet. But with each passing day, I get more convinced this was the right move. We still have a long road ahead of us, but with time, hopefully, Andy can start to learn more skills and have a better future. Isn’t that what any parent wants for their child?

Closing the Gap: Is Gene Therapy Our Future?

There are two thoughts that ran through my mind when our doctor told us that our son had a rare genetic mutation:

  1. Which one of us gave it to him (or was it both of us)? – and
  2. Why can’t they just replace the gene with the correct one?

While the answer to the first question may be easier to answer for certain diseases and disorders such as hemophilia and color blindness, others are not so obvious. Does it even really matter?  Both of our children have it and while that in itself is extremely rare, it doesn’t change how we treat it or how we go forward with our research. The second question, however, it just a little more complicated.

For many people, when they hear the term genetic mutation, a picture of X-men may come to mind.  For others, they may bring up images of two-headed frogs or disfigured children from the Chernobyl accident.  But not all genetic mutations are so obvious, and a small percentage of mutations are not even harmful at all.  So when a child is born with a genetic mutation that causes a disease, one potential treatment that is being tested with today’s technology is something called gene therapy.  Gene therapy, in essence, is an experimental treatment where new genetic material is introduced into the body by the way of a vector, the most common being viruses that have been inactivated.

When a disease is caused by a single genetic mutation, that is, one specific gene has a mutation at a specific location, it is considered a monogenic mutation.  This is what our kids have.  Their type of diabetes is caused by a single mutation located on the gene that tells the potassium channel how to act.  In their case, the channel remains in the open position, where a normal person’s potassium channel will open and close in response to the amount of sugar in the blood stream.  Hence the title of this series, Closing the Gap. One thing that has intrigued me through the years of dealing with this is the possiblity of gene therapy.  Why can’t it be just as simple as going into the cells and replacing the mutated gene with the correct gene?

According to Gene Therapy Net, there are currently 248 clinical trials for disorders and diseases with a monogenic cause (what our kids have).  The bulk of these clinical trials are treating well-known disorders like cystic fibrosis, hemophilia, muscular dystrophy, and severe combined immunodeficiency (SCID, aka “bubble baby syndrome”). There are scatterings of other diseases and disorders, but I doubt ours will be on any doctor’s radar for a clinical trial of gene therapy any time soon.  One of the most surprising discoveries I found was that the vast majority of clinical trials are happening in the US alone (over 1500)! While that is encouraging, gene therapy is still very much in its infancy, but at least those big pharmaceutical companies are starting to take notice and put their money into research and development.  There are conferences taking place all over the world now with some speakers from well known companies such as GSK (GlaxoSmithKline), Pfizer, and even a division of GE Healthcare.

So maybe we are still years out from being able to use gene therapy for our own kids, but at least science is starting to move in that direction.  Maybe one day, I will put my own passion to work and discover a way to join the ranks of the scientists and work toward fixing that gene.  Who knows, maybe the future is not so far away after all!

Closing the Gap: What the Research Says

Disclaimer:  The information shared in this post is in no way meant to be a diagnosis or treatment for you or your child’s condition.  Please know that our only intention is to share our story and help others see how we have advocated for the care and treatment of our children with a rare disease.  Please consult a physician for the care of you or your child’s specific condition.

One of the best parts of going to Chicago every few years is learning about new research in the area of Neonatal Diabetes, and last year was no exception.  While we were there, attending small group meetings, holding discussions with other parents, and talking to the doctors, we were told about an article that held hope for a small group of patients in our little circle of ND.  This article we read basically showed that a researcher was able to close the potassium channels in cells with mutations that previously kept the channel open.  What was so important about this was the drug used was an anti-epileptic drug, so by definition, it works in the brain.  Up until now, we have been playing a guessing game of increasing glyburide (a sulfonylurea) in an attempt to get a dose high enough to cross the blood brain barrier.  We have had some success and seen some improvements in learning, but it’s not as significant as we would hope.

So we came back from Chicago, hopeful that we could get our neurologist to prescribe this new medicine and see if we could get better improvement on it.  However, it was not as easy as just showing him the article and getting the drug.  While he agreed with the theory, he was visibly uncomfortable with prescribing this drug.  You see, the side effects of giving a kid with absence seizures carbomazepine is that it can cause them to have grand mal seizures.  Something our doctor, unfortunately, has experienced first hand and he didn’t want a repeat performance.

So we went back and forth with our neurologist, also getting our developmental pediatrician and pediatric endocrinologist involved in the discussion.  They were both on board and agreed that, in theory, it should work and the benefits would outweigh any potential, short-term, side effects.  There were, of course, other side effects we would have to consider.  Because this medicine works on the potassium channels in the brain, would it then also close the potassium channels in the body?  And if so, would we have to decrease the glyburide to prevent low blood sugars?

Potassium Channel (K+) is constantly open in our kids’ mutation. We need to close that gap in the brain to see increased learning.

Fast forward to the end of February and Andy had, for the first time ever, a prolonged cluster of absence seizures, one right after the other for over an hour while at school.  We ended up in the emergency room, got some blood work done (that was fun with a sensory, non-verbal kid who is 70 pounds of muscle!), and basically got sent home with a rescue medicine in case it happened again.  Which it did.  And the medicine did not work.  So I think all of this prompted our neurologist to decide to try the new medicine.  At our recent appointment, he said, we obviously need to make a change in the medicine since he’s having break-through seizures, so “we might as well try it”!

So here we are, getting ready to try this medicine that only 2 (maybe 3?) other children with our same syndrome have been on.  There are no official studies to tell us what to expect.  We are, in essence, patient zero.  We will get some baseline testing done to see where his IQ is, his present levels of reading and math and overall behavior and self-help skills, etc.  Then we start the medicine on Friday.  If it works, we will possibly start Katie on it too in 3-4 weeks.  If not, we continue to search for other answers like gene therapy (not so far off according to this article).  Of course, nothing is as cut and dry as we would like to think in medicine.  There are so many other factors to consider, so many other variables that we cannot predict.  Only time will tell.

The part that is so scary about having this rare disease and being the “pioneers” in paving the way with a potential new treatment is the unknown.  I am afraid of him having a grand mal seizure and me freezing, not knowing what to do.  I am afraid that I will be biased and think I see improvement, where there may be none.  I am hopeful that he will see improvement, but don’t really know what that will look like.  I know that it will not be an obvious change like when we transitioned to the glyburide.  There will be no celebration moment, like when we disconnected his insulin pump for the first time, declaring success and knowing he would now be insulin free!  It’s not going to be like the movie Awakenings, where the catatonic patients all of a sudden wake up and start talking and seeming “normal”.  It will be a slow process.  But if it makes his life better, it will be worth the effort and the fight we just fought for almost a year to get here.