hear me rare

I realize it has been quite some time since I posted. But there has been a lot going on in the background, and we are so excited to FINALLY share some really BIG news!

I promise I will post a more formal update on Blaise’s progress since last November. He really has been working hard at therapies and has come a very long way since my last post! BUT, the big news is… BLAISE STARTED AN INVESTIGATIONAL NEW DRUG!!!!

So the back story….we have been in contact with a drug company called Applied Therapeutics since February 2020, shortly after Blaise’s diagnosis. If you recall- my way of coping with the diagnosis was reaching out to family support networks, and Carl’s was digging into the scientific literature to see what the options were available for treatment. So in his research, Carl found an article that a drug class called aldose reductase inhibitors (ARIs) showed improvements in PMM2 in worm and yeast models. (Insert Pharmacist Education Session- how do ARIs theoretically work in PMM2-CDG?! ARIs are thought to increase the PMM2 enzyme activity.) His research then continued and he found Applied Therapeutics, who was utilizing an ARI which they call AT-007 to treat another rare disease called galactosemia. We reached out to the company to inquire if they had any plans to expand their use to PMM2-CDG. I suppose the rest is history.

Fast forward to early 2021, when Applied Therapeutics and Blaise’s geneticist at UNC agreed to take on the challenge of submitting for a single patient compassionate use IND (investigational new drug). For those who do not know this terminology, the FDA will occasionally grant compassionate use IND for patients with a disease or other life threatening condition that has no known treatment or for which all existing treatment options have been exhausted. Consider it the FDA Hail Mary 😉 If the IND is granted, the patient can receive an investigational new drug (sometimes it is FDA approved in another condition, or it might not be FDA approved at all) in a clinical trial type format. However, submitting for this is no easy task- it takes an enormous amount of time and effort to get to actually starting an investigational drug trial.

However, after an incredible amount of hard work and collaboration, ups and downs, we are thrilled to share that Blaise received his first dose of AT-007 last week! He is the first person with PMM2-CDG to receive this drug. Although Blaise received his first dose, we are in a dose escalation phase. We will start at a very low dose and gradually increase over several months to the full dose. This gradual escalation is to ensure there are not liver side effects, as Blaise (like many with PMM2-CDG) presents with some baseline liver abnormalities. So we do not expect therapeutic benefit from the drug for a few more months. Also, both my mama AND pharmacist cup were full when I got to mix the medication and give it to him! Luckily it wasn’t too complicated- just an oral liquid suspension!

We cannot thank Applied Therapeutics and Blaise’s genetic team at UNC enough for all of their collaboration and hard work to make this happen. It has been quite the journey for all! We are also incredibly grateful for all of the prayers and good vibes that we have received from family and friends. Please don’t stop now! We have 12-15 months on this journey. But we are honored and blessed to be a part of this little piece of history. Most importantly, we are very excited to see where this journey leads and opportunities it might create for others with PMM2-CDG and their families. 

If you would like to read more about Applied Therapeutics commitment to PMM2-CDG, click here: https://www.appliedtherapeutics.com/patients…/pmm2-cdg/ (also…there is a patient video posted there with a few folks you might recognize!)

If you have any questions or would like to contact Applied Therapeutics for more information, please email [email protected]

Despite it being 2020 and some days/months feeling incredibly long, overall time still flies. I think it is true what they say about kids…the days are long but the years are short.

Sometimes it is difficult to provide frequent updates about Blaise- because truth of the matter is- while we celebrate his victories (both small and large), the journey to get there is not fast, nor is it always linear. So if I were to provide, let’s say weekly, updates on Blaise’s progress, I would likely be reporting the same things over and over for some time.

I have been thinking for a few months now about how I categorize the (seemingly) long road to milestones for Blaise- and I have finally landed on how it feels as his officially unofficial physical, occupational, and speech therapist. There are three steps to a milestone: the Grind, the Climb, and the Landing.

THE GRIND

This stage is the worst. This because it is the hardest for all involved and met with the most resistance from our little man. This is also the least documented stage because there is so much hands on work (no extra hands for videos or photos) and tears from Blaise. There is certainly a lot of frustration- and it lasts for an unknown period of time. We are in this stage anytime that Blaise is starting to work on a new skill. For example, we have been working very hard on his weight bearing and walking, while using his AFOs (Ankle Foot Orthotics) and SMOs (Supra Malleolar Orthotics). It takes two adults to facilitate this movement. Blaise generally likes to behave as if his legs do not work. He uses his upper body to drag his lower body everywhere. So you can imagine trying to make him stand AND move his legs while wearing orthotics does not come without a lot of resistance from him. It also seems that when we are in the Grind- there are multiple skills that we are in the grind for all at once. This is especially frustrating because no matter what skill you work on, there is no reprieve. He hates them all (thumbs down button to the max). Most recently our grind skills have been walking, standing, four point crawling, and communication.

THE CLIMB

While the Climb isn’t as emotionally draining as the Grind can be, it is still sometimes frustrating because you never know how long this stage will last either. However, during this stage, Blaise starts to master a skill, and doesn’t cry or resist as much when practicing the skill. For example, with walking he can start going longer distances before he is too tired to continue, he requires less prompting and help in moving his legs, and can move faster without breaks every few steps. As it relates to communication, he will require less prompting before communicating, or might even communicate without any at all- just not on a consistent basis. The Climb lasts for weeks and even months at times, until he can perform the skill on a regular basis (then he graduates in my mind to the next stage). This doesn’t discount the “little wins” that Blaise has on the way to the next stage. We find some days or weeks Blaise does better than others, so when he does something at 100% one day, that might not be the case two days later. Some days Blaise is more unsteady than others, more tired than others, more distracted than others- but hey, who isn’t?! I would say we have been in our most recent Climb for a few months now. Here are a few videos of Blaise’s “little wins” to date!

THE LANDING

You might wonder why I call it the Landing and not the Peak? He hit the milestone, we should celebrate it instead of giving it a name that is kind of “blah”. While I am over the moon when we hit a milestone after lots of hard work, (I usually say Blaise is “making waves” when he gets there), I call it the Landing because the work isn’t done. It is just time for new work- and we are about to be back in the Grind. I liken it to climbing a mountain that is very cloudy at the top. You climb and climb, and finally reach the clouds- only to find out that the mountain actually continues up for quite some distance. You haven’t reached the peak, just a landing on the way to the top.

I think that these steps are not only the case for Blaise as he works on his skills, but probably for all of us as we go through our lives. In many cases- it is easier to call the “Landing” stage a “Peak”. Why? Because it is easier to say “I have hit my goal” and to bask in that fact than it is to then make a new goal, knowing you are back in the Grind. It is hard to go from the top to the bottom. But that is how we improve and get better. So I suppose we can all take a lesson from Blaise- because the work NEVER stops for him. And really, that is true for most kids. It is only after we get degrees and start jobs, and maybe families of our own, that we tend to lose that fire in our bellies. Here is your wake up call.

And also some adorable pictures from Blaise to assist in your motivation:

Since several of our vacation plans earlier this year were ruined by the pandemic, we were looking forward to Carl having almost a full ten days off and spending some time just the four of us at the beach! Unfortunately, our family vacation can enter the history books the way the rest of 2020 will…on a scale of 1 to 5 stars, it will get a negative twenty.

To start things off, we were supposed to leave for the beach Monday morning, but were delayed a day because of Isaias upgrading from a tropical storm to a hurricane and then turning itself straight toward North and South Carolina. But no big deal, we got some extra things done around the house and Blaise had some extra therapies before we headed out.

We arrived on Tuesday, and Blaise had been a little out of sorts since Carl’s vacation started, but he had several teeth (even molars) coming in all at once and we assumed he was cranky because of the teething pain. After all, ibuprofen seemed to get him back to feeling like himself and we even got our Blaisey smiles during our first walk on the beach!

Unfortunately this afternoon stroll was about all we saw of the beach, because the rest of our time there it was pouring rain, thundering/lightning, or it was time for naps so we didn’t get to enjoy the sand and the waves as we had hoped. V did have an excellent time feeding ducks and turtles though, so I suppose there is some silver lining!

As the days went on, Blaise seemed to continue to get more cranky, exhausted, and not eating as well. It isn’t unusual for Blaise not to eat as well when we travel, and he still seemed to be bothered by teething. We even brought an otoscope to check his ears and make sure he wasn’t getting an infection secondary to his teething, but his ears continued to look perfectly healthy! He just wasn’t himself. He wanted held all of the time and we weren’t seeing those sweet smiles.

On Friday morning, Blaise slept in, was having staring spells and was crossing his eyes more than usual. He didn’t eat much, and even when he was being held, he was upset. We decided to pack up early and head home so he could be seen by the pediatrician the following morning. Of course, the day we had to head out was the nicest weather of the week…oh well.

Upon arriving home around 6:30 pm, I went to get Blaise out of his carseat and he was on FIRE. Not to mention he just didn’t look right at all. He was lethargic, kind of limp, and his color was off. Shortly after I left to the ER with him.

We found out he had a temperature of 104.2, a very high heart rate, and drew some labs. It is always interesting meeting new medical staff with Blaise because no one knows about PMM2-CDG, and I end up having to educate them a bit and provide input into his plan of care (like he has baseline liver abnormalities, let’s give him ibuprofen instead of Tylenol). It is also difficult because he looks typical and generally is pretty pleasant, so at one point there was discussion of just giving ibuprofen, waiting for his fever to go down a bit, and not drawing any labs (because they didn’t want to stick him, I think). Thank goodness we didn’t go with that plan- with a special shoutout to Nana and Dad for being the strongest advocates for Blaise from a distance. Because of COVID, I was the only one allowed to be with Blaise in the ED. But I was communicating with them regularly and their expertise helped make certain that Blaise got what he needed that day.

Brief soapbox alert (skip to the next paragraph if you don’t care about my soapbox 🙂) : I cannot emphasize enough to any parents, especially those whose children have a rare disease, to SPEAK UP if you don’t agree with something that the medical team is doing. It can be awkward to do so because they are the professionals and you don’t want to step on their toes- but YOU know what your child is like on a daily basis and YOU know when something isn’t right. Especially for these zebra babies, most medical professionals aren’t well versed in the disease state and you are going to be the educator. Your child’s medical emergency is not the time to lose your voice. I think sometimes medical professionals are jaded by parents who severely overreact- like their child coughs so they must have cancer (yes, these people do exist). But don’t let someone talk you into something you know isn’t right. For example- not drawing labs on Blaise that day and just going home could have had a really devastating outcome.

Now that I’m off of the soapbox- back to the story. Labs came back and his liver enzymes had doubled and tripled from his baseline. We gave a fluid bolus and antibiotics, and prepared to get an ambulance to take him to UNC. This whole process took several hours, but that is the short version.

We arrived to UNC by ambulance just after midnight on Saturday morning, and were directly admitted. We gave Blaise some more ibuprofen, and his temperature finally broke 100. We obtained another set of labs and a respiratory panel, and started maintenance fluids. COVID test came back negative (for anyone wondering :)) as did the rest of the respiratory illnesses. However, his liver enzymes that were already elevated increased significantly and had since quadrupled again. This prompted more labs, consults, and an abdominal ultrasound to see what his liver looked like.

As I mentioned earlier, Blaise was having some staring spells earlier on Friday and we were worried about seizures. So he was ordered to have an EEG, and had a lovely hat overnight going into Sunday morning.

I won’t go over every last lab value and consult that Blaise had, but long story short, Blaise got better every day. His liver looked good and healthy on ultrasound, his enzymes started decreasing, and the EEG showed no seizure activity. Blaise started playing, and eating more by Monday morning and we were able to leave later that day. We later learned that Blaise tested positive for a pretty common virus that most people fight off without any issue, but it sent Blaise’s immune system into a tailspin.

There are so many people to thank who helped us during this very scary and difficult time. I appreciate Blaise’s geneticist answering my texts and taking time away from her vacation to talk with me and Blaise’s medical team and helping them with the plan. I appreciate my local family being able to help make sure V was distracted and taken care of while I was at the hospital and Dad had to work. But most importantly, I cannot thank everyone (you know who you are) who prayed tirelessly for our little man. I know those prayers were heard and that is why Blaise is where he is today. In fact, Blaise came home and in true Blaise fashion, started doing new tricks the same day.

We have been living in this magical land thus far with Blaise in that we haven’t experienced a significant event like this. I know other families in the CDG community unfortunately deal with these on a more regular basis. But now that he has, we have learned from it and have made some changes for the future. We added additional “allergies” to his list (because of liver abnormalities) and got some items to put in a “go bag” for unexpected hospital stays. We also will be creating an “emergency plan” that we can just give to any provider that needs to care for him. I highly encourage all parents in a similar situation to do the same. It will cut out a lot of the questions when those who are unfamiliar with your child are trying to come up with a plan. One thing I know for certain as it relates to this event, is that hindsight is 20/20 (pun intended?…. you decide).

Our last update on Blaise’s progress was at the end of March. So many things have happened since then! The last update included Blaise eating some soft solids, drinking from a sippy cup with assistance, and getting up on all fours by himself. Here is all of the progress Blaise has made to date!

In our last post, Blaise needed assistance holding the sippy cup and also getting food to his mouth reliably. Now, he can drink from his sippy cup and feed himself! In fact, most of the time when I try to feed him now, he whines and wants to do it independently. This seems to happen when V is also eating- so I guess he might be more competitive than we thought!

This year I received THE BEST Mother’s Day gift a gal could ask for….Blaise started crawling!! He is army crawling, not on all fours yet, but is mobile and is into everything! V was quite surprised when Blaise could ruin the puzzle he was putting together and moving it out of arms’ reach was no longer effective! It is pretty remarkable to be cleaning up the kitchen and I turn around and Blaise is on his way to come and see me. That is something I wasn’t sure would ever happen, or if so, when.

Blaise has been working SO HARD on physical and occupational therapy. One of the goals that we have working toward is getting Blaise to sit for an extended period of time on his own. It has been so difficult to help him build strength in his trunk/core, and unfortunately a strong core is what will help him advance with other skills. His therapists suggested this shirt- called a SPIO- to help provide some extra support and input in his core. You can think of this shirt as having scuba suit material but fitting like a tight compression t-shirt. I like to call it his “super suit”. He wears this shirt underneath his clothes everyday. And I cannot believe the difference it has made in his strength and abilities! About three weeks ago, I turned around and Blaise was sitting up tall- all by himself!! I couldn’t believe it, and I had left him on his belly. So even though Blaise still gets tired and falls down face first on occasion, he is really coming a long way. Now he is sitting up faster on his own, for longer periods of time, and can even sit when he isn’t wearing his shirt.

Blaise also has been enjoying doing therapy while standing, although his standing posture isn’t great. He hyperextends over his ankles, won’t bend his knees, and curls his toes. He does these things to give himself an added sense of stability, however- that is not how he can realistically stand. So Blaise has been fitted for braces that will arrive soon, and hopefully help correct his standing. Once we fix his standing- fingers crossed we can move on to standing mobility!

Blaise recently had his eye follow up. I’ll admit I was ready to be scolded by his doctor because I have not been forcing the issue of his glasses. It’s just that since he has been able to use his hands better, every single time I put on his glasses, he pulls them off in seconds. For awhile, if you were holding him he would keep them on, but that didn’t last too long. I reluctantly told the doctor that he was not wearing his glasses at all, that he just wouldn’t keep them on. The doctor told me she wasn’t at all surprised that he was ripping them off. When she said that I laughed but also was curious why she said that. Was it just because he was a toddler and wasn’t going to keep anything on his face? She went on to tell me it is because his eyes have improved and he no longer needs them. I couldn’t believe it! Anecdotally he has been crossing his eyes less than he used to, but I had no idea that it would translate to actual clinical improvements in his sight! We couldn’t be more thrilled! The only downside is that there won’t be any more cute baby pictures with glasses- so sorry in advance 🙂

So moral of the story is- we might as well start calling our little man DJ Khaled- because all he does is win!

Since Mom has been doing all of the talking…it is time for Dad to have a “celebrity shot” on the family blog. So here it goes…

I remember the moment I knew something was wrong with Blaise. It was a gut-wrenching feeling, suspecting that there was something going on with my child that I couldn’t understand, much less fix. It was the week before Christmas 2019, and my parents had come to visit my family for a few days while I was working nights at the hospital, before we all flew together to meet up with my siblings and their families. That week I had spent my nights searching the web for something that might explain my Blaise’s behaviors. During my research I was confronted with the realization that he was clearly not meeting his developmental milestones. Wanting to test my hypothesis, one evening I carried Blaise away from the rest of my family and any distractions. I laid him down on the ground on his back, grasped his hands, and slowly pulled his shoulders off the ground bringing him towards a sitting position. He lay there as I pulled, body mostly limp, head and neck extended behind his body with a huge grin on his face.  “How’d he do?” my parents asked. “Not good”. It was my attempt at a “pull-to-sit” test, and at 10 ½ months he was still displaying a head lag; something a typically developing child should have grown out of at about half his age.

That was the moment I knew something was different. It was also the moment I started wondering how I hadn’t noticed sooner. How could I have just noticed that my son hadn’t even met his 4-6 month milestones? Had I paid so little attention to him? Was I too busy with other things to notice my child struggling developmentally? A lot had happened in the past few months, including a move to a different state, moving into a new house, starting a new job. I felt guilty that I had missed something. But I wasn’t the only one. Our pediatrician had repeatedly reassured us that his development was still within the realm of normal, that the second child often won’t meet developmental milestones at the same rate as the older sibling. It was reassurance we happily accepted despite growing evidence that our Blaise’s development was anything but typical.

The next week was an experience of mixed emotions. I hadn’t spent Christmas with my whole family in years, and this was the first year my siblings and I all had children of our own to celebrate it with. Christmas is by far my favorite holiday, and I still can hardly contain my excitement leading up to Christmas morning. My family swooned over Blaise and his endless supply of chubby-cheeked grins, and watching all the young cousins playing together was priceless. But this year was bittersweet. Our family holiday introduced me to a concept that I hadn’t given much thought to previously, but one which I now am constantly reminded of. Teddy Roosevelt once said, “Comparison is the thief of joy”. While this is certainly not true in all contexts, I started to understand why people might believe it. Blaise was born just one week before his cousin, and seeing Blaise every day, it seemed like he was making very slow progress toward his milestones. But seeing the two boys side-by-side really served to highlight just how far apart they were developmentally. Any hope of Blaise’s slow progress being within the realm of normal flew right out the window.

Interestingly, the next month of specialist consults and frequent lab draws didn’t seem to affect my perception of the seriousness of Blaise’s developmental concerns. The developmental specialist and neurologist telling us that they were really concerned with his hypotonia and ataxia didn’t change much for me. In my mind I already knew there was something wrong, I was just waiting on the name. The abnormal carbohydrate deficient transferrin screening test finally gave us a clue. A referral to the geneticist quickly followed. And there was the name. Not an easy one at that. PMM2-CDG, or CDG 1a. Not easy to remember, or to describe to concerned family members and friends. But it certainly described Blaise, and all the atypical behaviors and development he had been displaying. 

Kara complements me so well in so many ways. We also have very different ways of processing information, and when that information is your son’s medical diagnosis, the differences become quite striking. While I was busy pouring over published scientific literature on everything CDG (scientia potentia est), she sought out information and support in other places. She joined the CDG Facebook group long before I could bring myself to do so, and she quickly connected with other CDG parents and families. When she posted to the group with an introduction to our CDG family, it caught me totally off guard. Somehow no number of lab tests or medical opinions prepared me for the realization that we were now “one of those families” that I had read about. 

Just like the realization that our son is not typical, the realization that our family is not typical continues to evolve and unfold. We continue to discover the multitude of ways in which these new realities affect our lives, and we continually pivot to address new challenges. Overall, we’ve made a lot of good progress. Blaise grows more capable every day, and we remain hopeful that his capabilities will reach their fullest potential. Maybe, someday, there might be a treatment, or even a cure for PMM2-CDG. With all the ongoing research into this rare disorder, that possibility doesn’t seem so far-fetched.

Blissfully ignorant of it all, Blaise still showers us with the toothiest, drooliest grins that can melt your heart. From time to time I still need to remind myself not to compare, and to appreciate what he is able to accomplish today that he wasn’t able to yesterday (a more constructive sort of comparison). Like everything in life, it’s still a work in progress. Some days hold more than their fair share of “what if’s” and “if only’s”. Other days we’re pretty darn content with how fantastic our life is. 

Coming home to a smile like this, it’s hard not to consider just how fortunate I am.

May 16th is the World Congenital Disorders of Glycosylation (CDG) Awareness Day! As this is coming up next week, I wanted to provide some information regarding how you can help support Blaise on this special day!

First of all WEAR GREEN on May 16th! That is the “official CDG color”. You know the boys and I will be rocking some green on May 16th. Don’t have anything green? What a GREAT excuse to spend some quaran-time doing some online shopping! Or wear your St. Patty’s day shirt. Blaise does have some Irish blood, after all!

As I am sure you know, raising awareness is crucial to the success in receiving resources to manage CDG, to continue developing potential treatments, and to (hopefully) find a cure for this disease. There has been a concerted effort to encourage the World Health Organization (WHO) to acknowledge May 16th as CDG Awareness Day. Right now, every single year, every state has to reach out to their governor and request this day to be officially acknowledged for CDG. In fact, I reached out to the NC Mayor in the Raleigh/Durham area and submitted information requesting a proclamation be issued this year acknowledging May 16th as CDG Awareness Day. But the reply I received was along the lines of “proclamations are not being issued due to staffing issues with COVID-19”. So wouldn’t it be nice if this day was already recognized so that a worldwide pandemic, or technological submission issues wouldn’t minimize the national awareness of this day?! I think so. If you think so too, PLEASE take a moment to sign this petition (http://chng.it/pwPt2gd9hd) so that we can make CDG Awareness Day recognized by the WHO and allow families of CDG to stop submitting these requests to their governor every. single. year. Please have your significant others, friends, children- anyone who can read and sign for themselves sign the petition! Now we are working toward 7,500 signatures!

Last October, the NIH approved a grant creating the Frontiers in CDG Consortium (FCDGC) (Here is more about the consortium if you are interested in learning more https://www.rarediseasesnetwork.org/fcdgc). The FCDGC has assisted in the creation of some great patient educational materials, which have been long overdue for the CDG community, Here is the link to these materials http://cdgcare.com/2020/05/05/patient-educational-materials-from-the-fcdgc/?fbclid=IwAR1JNkX_XTNhmJVg3lzQbyFqrZvoMT46v-bQdxgVyJblJQ4NKczH8YTEiBU These resources are a little longer (~20 pages), but very thorough, easy to read, and put together by staff at the Mayo Clinic!

Also, I was informed recently about this super cool infographic on CDG. I am all about easy to read and understand resources to teach people about CDG. I like that this infographic has a lot of simple but impactful facts without a lot of words! https://worldcdg.org/resources/infographic/what-is-cdg

As you know, one of my goals with this blog is to raise awareness of CDG. I want family and friends to know about this rare disease so they can better understand Blaise- and maybe even educate their friends and family. But most importantly, by raising awareness we support the ENTIRE CDG community (~1,500 strong.. and growing!). You might be thinking- Kara- that was a long and super boring blog post. So I will end with an adorable picture to make it worth your time: