A Rebel Alliance

No, I'm not talking Star Wars. 

I'm talking parents of rare children. Specifically, I'm sharing an update on the PIGN-CDG drug-repurposing project. If you don't have time to read much, then check out this update from Perlara: Research Update. If you have more time, continue on.

As you may be aware from prior posts, our rare community is researching whether existing known drugs or compounds could be beneficial in helping our PIGN children. You can read more about the initial scope of the project here: Drug Repurposing Fundraising Many of you have generously donated directly or supported AJ's fundraisers selling fidgets and dragons that he creates himself on our 3-D printer. (You can still donate directly here: Tax-Deductible Donation or order dragons/fidgets here: AJ's Fundraiser)

To greatly simplify PIGN-CDG, Teddy's body cannot process sugars on the most basic cellular level. If you recall sugar chains and cell processing from biology, well, kudos to you because I don't. But you can think of it like an assembly line in a factory that has a broken part that prevents most of the pieces from being perfectly assembled. They may be somewhat functional, but it's rare (no pun intended) that they are fully functional. This results in all the challenges our children face, from seizures to hypotonia to respiratory challenges to developmental delays and the list continues. Their bodies don't function right on the cellular level, which obviously impacts them as a whole. 

It doesn't stop Ted from enjoying flying fighter jets, though.

This also complicates potential treatments because all medications and treatments can be impacted as well by these faulty sugar chains and processing problems. Everything can be a bit (or a lot) off with our children. Combine that with the fact that there are approximately 100 known cases of PIGN-CDG, and well, it's understandable why there's no treatment for this disorder. We can only treat the individual symptoms (aka treat the seizures, manage the hypotonia, etc.) and do nothing to improve the overall health of our children. 

That's why this drug-repurposing project is invaluable. This ground-breaking scientific research is taking a huge bank of known medications and compounds to see if anything that already exists could be used to improve the overall health. This is a long, expensive process. 

But it's so exciting that we're seeing promising results. As Perlara's update shares, some families have been piloting ascorbyl palmitate and seeing improvements. This compound can be easily accessed without a prescription in many countries, though each family must still work through their medical team. We are a bit later to start due to the events of last year, but we have baseline labs scheduled in a week with a bottle of ascorbyl palmitate secured. (Hmm, that reminds me we need to take baseline videos of Teddy this weekend.) We will start him at a low dose for a month, monitor and recheck labs and then potentially increase his dose. 

While we don't anticipate any overnight, drastic changes, any improvements for our PIGN children are huge. You may read the research update and think, well, that's just normal developmental milestones - it could be just that the child is getting older and advancing. But our children don't follow normal milestones, and they lag months or years behind most, if they achieve them. So any progress noted in a couple months of trialing the compound is fairly reasonably associated with the compound (though we will leave that up to the scientists and doctors with baseline and other labs, video evidence, recorded seizures, etc.)

We're excited about what this could mean for Teddy. We're excited about what it could mean for all our PIGN families, both present and those who get this difficult diagnosis in the future. So the next steps, while we continue to fundraise, is that because it's an over-the-counter compound, we're able to pilot and trial on our own as families (similar to how we've fundraised) without FDA approval. Perlara is busy in the lab and will be testing the best hits, including this ascorbyl palmitate, on the DNA samples from various PIGN children, including Teddy. This is the next step to evaluate what works best with real human PIGN mutations (of which there are many). The hope is that we continue to make progress and do move to the point of FDA trails, whether for this compound we have now or something different. 

The science will take years, and we so appreciate your generosity and support. It's exciting (and expensive) to be at the forefront of medical and scientific research that will directly benefit others like Teddy.

PIGN Research Project Update

I wanted to share an exciting update regarding the PIGN drug repurposing project. I shared about the project previously on the blog here. For those unfamiliar, the quick explanation is that our PIGN community is fundraising to do the scientific work to determine if any existing drugs can be used to treat those with PIGN-CDG. It's a long, expensive process, but this scientific method has been successful with other illnesses or disorders, including very promising results with another type of CDG. Essentially, it's the best hope we have for any type of true treatment for PIGN in the foreseeable future.

To do this research, 10 genetic variants were selected to build yeast avatars to test against existing medications. These variants represented a wide range of the known PIGN defects and were selected to represent a wide range of defects and because they were easily modeled in yeast cells. We knew Teddy's variant wouldn't be selected because it's not easily replicated due to part of his variant being a splice site, meaning his gene split apart and reattached in the wrong place. (Whoops, he inherited that from me.)

Additional variants were selected to be part of a second phase of research. That group of variants will be used to test the drugs selected against human cells, as opposed to yeast avatars. Teddy was selected to be a part of this research group, as it's simply growing cultures of his cells to test the different medications.

This meant Teddy needed a skin biopsy done. He's had this procedure done several years ago, as part of his NIH natural histories study, but he was sedated because other tests were done at that time. This time required several weeks of coordination with Mayo Clinic and local providers leading up to the actual appointment.

He had his biopsy done Monday, and it went remarkably well all things considered. (All things include the fact that it required 3 of us to restrain him while the puncture was done, and there's a whole separate saga about hives, urgent care visits and the like that occurred later in the day.) 

Teddy had a lot of opinions on where I should sit throughout his appointment.

So his sample is being sent to Mayo Clinic for storage. His cells will be replicated in laboratories to test against different medications. The goal is to see if a medication that works well in multiple yeast avatars works well in the human cells, along with testing a wider range of mutations. (Unfortunately unlike something like Down's syndrome where the mutation is universal, CDG-PIGN encompasses a wide range of mutations, many similar but relatively few completely identical.)

While it was tough to have Teddy endure a skin biopsy that's technically not needed for diagnosis or treatment at this time, we recognize this act can benefit not only potentially Teddy but hundreds of other families with this disorder down the road. It's a small sacrifice to benefit the greater good. (And as we already lost another one of our PIGN kiddos this year ... it's January 18 ... it's the least we can do.)

We'll be continuing to fundraise as science isn't cheap, and this is very much a grassroots campaign done by the families affected. We're small, but mighty when combined with caring friends, family and those who support our journeys. 

If you want to make a donation, you can do so here: https://teddystriumphs.blogspot.com/2022/06/pign-cdg-research-were-fundraising.html 

The Science Behind PIGN-CDG

Teddy visited Dr. Morava at Mayo Clinic today for his first annual follow up. She is following him through her natural histories study, and we're so grateful for the opportunity to see and consult with her. She is a world-renowned expert in CDG, and she's absolutely brilliant. She's also phenomenal with Teddy and takes the time to explain things to us in a way that makes sense ... as much as this highly scientific stuff can.

So I'm going to use this blog post to summarize what we discussed, both for the benefit of other PIGN-CDG families and our family but also to help cement the information in my brain. My warning is that this is my understanding and recollection, so anything inaccurate is clearly my error. 

Dr. Morava provided us a chart similar to what she used last time and covered again the basics of GPI-anchoring disorders. Each cell uses sugar chains to build antennas that have protein on top. That is how cells communicate and function together at the most basic level. PIGN-CDG right now is the at the 7th step in the process of building of the sugar chain, with I believe 18 GPI-anchoring CDGs known. So, essentially Teddy's cells start building the sugar chain but stop before the chain is complete. That is why Teddy is globally affected because his brain's cells can't communicate and execute as intended without the proper antenna structure. 

As she explained before, it's a tough diagnosis to develop treatment for because the sugar-chain building occurs deep inside the cellular level, and it's a very specific need. You can't simply provide more of the sugar molecules needed because that's like trying to shovel more snow with a broken shovel ... more does you no good. 

She's aware of the drug-repurposing research we are pursuing with other PIGN-CDG families. She thinks that is a very good thing, not only for PIGN but also for potentially other PIG CDGs and GPI-anchoring CDGs. The goal with the GPI anchor disorders will be to target drugs that can cross the blood/brain barrier, as that is where they will need to do their work. 

Dr. Morava is extremely familiar with drug repurposing, as she is involved with drug repurposing for the most common CDG, PMM2. They started approximately 4 years ago and are just now approved for clinical trials. Believe it or not, that's extremely fast for the use of a drug. They actually got rare direction from the FDA to skip phase 2, which is an extended study of the safety of the drug in patients, and move right to phase 3, which is a controlled test with both drug and placebo. Dr. Morava explained there's both pros and cons to that situation, and it's not the normal process but happened due to the known safety of the drug as it's been in use for 40 plus years. In the PMM2 study, they saw improvement in the earlier testing in about 80% of the cases. They started with yeast cells, just as we intend to, and then moved on to worms and then skin biopsies. 

Dr. Morava said that with drug repurposing they can test 200 known drugs at a time to work their way through the 2,000 FDA-approved drugs. There is a difference between what is approved in the US and what is approved in other countries. So clinical trials may not cross country lines perhaps, but they can do work in parallel with other countries. For example, there are some studies where they hand off the different stages. This can be helpful as there are limited CDG experts. In the US, there are 4 (Dr. Edmundson in Philadelphia, Dr. Lam in Seattle and Dr. Scaglia in Baylor whose plate is full, in addition to Dr. Morava). 

Dr. Morava said one of the challenges with drug repurposing is identifying the biomarker to test. One possibility may be the truncated GPI anchor, but they need to identify something they can clearly measure in each of the tests to see if there's improvement with each drug. 

Another type of potential treatment aside from drug repurposing that does get a lot of attention is gene therapy. There's excitement over that possibility for PIGA as that type of gene therapy already exists in animal models for that gene. If you've heard of CRISPR, that's gene therapy. Essentially gene therapy changes your genetic makeup forever, which is great in the sense of correcting a damaging mutation. However, the long-term impacts aren't known yet because it's such a new therapy. There is the possibility that the genetic rewrite to fix one gene may create other issues, so Dr. Morava cautioned that while it may make sense for diagnoses with no hope, she doesn't view it as the best option for PIGN, particularly individuals like Teddy who are doing well.

The last type of potential treatment we discussed is the idea of using MRNA, which would essentially be temporary genetic therapy. You've all heard of MRNA, as that's how the COVID vaccines were developed. The idea with MNRA is that you inject the correct version of the gene to build the sugar chain and protein correctly. The advantage of this type of therapy is that it should work on all PIGN individuals, regardless of the specific and different mutations. (That's one of the weird things about PIGN is that most of our children have different mutations ... they're all messed up but in a lot of different ways.) The reason is you're simply overwriting whatever the error in the code is with the correct code. The disadvantage of MRNA is that it's temporary. It only lasts about 2 weeks, so it would be a continual process. However, that's also an advantage in the sense that if detrimental side effects are noticed, the process can be stopped and things go back to baseline. (Although Dave and I talked about how incredibly hard it would be to see progress and then regression.) 

The MRNA is being tested in terms of proof of concept with a glycogen storage disease. It's not a type of CDG, but it is another glycosylation disorder. It will be interesting to see and learn what happens.

Of course, all these treatments are literally years down the road. But it's exciting that science is happening, and that people are interested in GPI anchor disorders and these types of CDGs. That's the biggest challenge is finding the right people to be interested and champion for our children by doing the work. 

The main focus Dr. Morava has currently in her research is biomarkers to diagnose CDGs with a biochemical diagnosis rather than a genetic array that results in likely pathogenic results. Right now we have a likely pathogenic result for Teddy from his genetic testing that indicates that his PIGN mutations are likely the cause of his symptoms and disorder. Her focus, with a study of 200 patients, is to develop a blood test that will provide a functional diagnosis for CDGs. This would also, at least in my mind, provide biomarkers that can be used in further research, drug testing and treatment development.

Whew, that is my entire page of notes around the very complex chart she provided, in addition to the much simpler GPI anchor chart she gave us. I haven't touched the 20-page booklet of GPI Anchor Disorders: A Subtype of Congenital Disorders of Glycosylation, but I will. Also, as soon as I get a digital version of that, I'm happy to share it with you if you're interested in learning more (and will share it on our PIGN page.)

Teddy loves to visit Dr. Morava ... and he "locked" the dietician in the corner. 

CDG World Awareness Day 2022- AJ's Version

Hello to all reading this letter. This is AJ.

Happy CDG World Awareness Day!!  I'm Teddy's big brother, and I was thinking "What would my life had been if Teddy was normal?" Well, Teddy comes with pros and cons. 

Pros: 

• Amazing brother
• Always has a smile
• Never would have met so many cool families with CDG-PIGN (Congenital Disorder of Glycosylation-PIGN variant)
• We would have never gotten amazing babysitters (Bri and Sigrid)
• And so many other things Teddy has given us

Cons: 

• Would never have to deal with research studies and tests 
• Life-threatening seizures
• Teddy harassing me
• And him causing trouble

Teddy is a one-of-a-kind gift given to our family. " So, what would my life be?" you ask. Well, it would be totally different. So, Teddy's proof that anyone can be amazing and make a difference no matter what religion, skin tone, disability, problem, or differences they have. Teddy is a gift in his own way, and nothing will change that. Because of Teddy's disability, my mom's been able to help so many other families with CDG-PIGN. 

Sincerely,

AJ Blondheim

CDG World Awareness Day 5/16/2022

CDG World Awareness Day 5/16/2022

PS. The cookies were made by mom. If you want some of these or other delicious things, you should email to get in contact with Kerry at nonesuchbakeryllc@gmail.com

PSS. All the pictures were taken by me (AJ).

World CDG Awareness Day - 2022 Version

It’s World CDG Awareness Day! Each year May 16 is the day that worldwide we show our love for all those with CDG and spread as much awareness as we can. The reason why awareness is so crucial is that, like most of you, we had never heard of CDG (Congenital Disorders of Glycosylation) before Teddy’s diagnosis in November 2015. We were informed his initial diagnosis of Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 1 (MCAHSS1) was a type of CDG. CDGs are classified as rare diseases as a whole, and there’s more than 100 different types of CDGs known, with more discovered as science continues to evolve.

I think we need a new picture. This one's a few years old. 

CDGs are the result of genetic mutations that impact how the body processes sugars on a cellular level. (Think back to high school biology.) Since it’s on the cellular level, there’s no dietary changes to make. Unfortunately, there’s also no treatment, let alone cure. Instead, we treat the symptoms that present with CDG, which means for Teddy we treat for seizures, low carnitine levels and assist his body with getting much needed rest. (Yes, some of the medications we use help Teddy sleep because he struggles with sleep, which makes him cantankerous and more prone to seizures. As an added bonus, these medications also have seizure-reducing properties.)

Teddy’s diagnosis was updated to CDG-PIGN after the medical community changed the naming system to reflect the name of the gene that is impacted. When Teddy was diagnosed, we were told he was likely the 15^th person in world with this diagnosis. Our kid wasn’t one in a million … he was more like one in a billion.

In the past 7 years, more have been diagnosed with CDG-PIGN, primarily children, although the oldest in our group are in their early 30s. That doesn’t mean the life expectancy is 3 years, like the first medical research papers we received, although the reality is that this diagnosis impacts people in a way that can dramatically shorten their lifespan. This diagnosis also didn’t exist until 2011 and requires expensive testing to lead to a probable diagnosis (as there’s no blood test to confirm yet). I’m certain there’s older individuals … and far more than we know of … who never got a proper diagnosis.

As it stands, our group of known cases has grown to almost 100. One of the amazing PIGN moms, Ashleigh, invited all who wanted to join in a video compilation. She kindly gave me permission to share her video. CDG-PIGN impacts each person differently, even siblings, yet our children have amazing spirits and smiles, resilience and determination and manage to change the world with their existence. I’ve shared past posts introducing a number of our PIGN families in past years here and here and here. Our group continues to grow, and our hearts ache for our community when we lose one of our children. Unfortunately, that happens every year, and it hits home each time. The names with the doves by them are no longer on this earth.

As you can see, there’s a wide range of how the disorder affects our children. Generally speaking, the primary challenges are verbal communication, developmental delays and seizures. The severity of the disorder varies greatly as we have some individuals who’ve had only a handful of seizures and others who seize more than 100 times a day. There’s children who can run and walk, like Teddy, and others whose challenge is head control who require total assistance. Some of our children are incredibly medically complex and receive hospice support, and others thankfully are thriving without frequent doctor visits.

Like I said earlier, there’s no cure or treatment currently. However, there is a glimmer of hope for treatment through genetic treatments like CRISPR or, more likely, drug repurposing therapies. We recently had a meeting with a handful of other families to discuss the possibility of starting the science for a potential treatment for our PIGN children. (I’ll share more on that in a future blog post.) And that’s why today is important to families like ours.

Without awareness, the only ones interested in treatment are the families impacted. Since we have less than 100 families in our group, that’s a really small group interested in treatment. The more awareness we raise, the better the chance of finding others with a similar purpose, getting doctors and scientists interested in CDGs (including PIGN) and potentially raising funds because science is expensive.

So, feel free to share this post with others to introduce them to CDG-PIGN. Awareness starts with sharing our story.

#WorldCDGDay

Lifestyles of the Rich and Famous

Maybe rich is an exaggeration, but Mr. Teddy has finally made his way into research papers! So he's clearly famous. OK, maybe famous is an exaggeration as well, but this has been 5+ years in the making. 

When he was first diagnosed, the genetics team was excited about his case, the rarity of his diagnosis and his notable differences from some of the earlier research papers that painted a bleak prognosis. They wanted to write a research paper, but indicated it was a process that could take longer than a year due to limited resources. Let's just say that never came to fruition.

Then there was a person who was presenting a paper about Teddy at a conference, and we were so excited that his information would be shared to help educate others. Then a minor thing like a global pandemic cancelled that conference, and that never came to fruition. (Or we never saw or heard the final report, if the individual was able to present it.)

The other week a family in our PIGN group shared a research paper they had received, and another parent asked if it was the result of the NIH natural histories study because she recognized names of researchers. Sure enough, as I read the paper and the case studies, Teddy's profile from NIH perfectly matched.

So he finally is included in research, representing who he was already 3-4 years ago when we were at NIH. (There's a whole series of posts on the blog about the intensive testing done there if you want to know the details.) 

Unless you have access to medical research libraries, you likely won't be able to find the 2022 publication of PIGN Encephalopathy. But I can send you a copy if you're interested in reading it. Unfortunately, though, unless you possess significant medical background, you probably won't find much value in it. We learned early on that reading any medical research involves looking up the definition of approximately every other medical term because they are written in jargon not understandable English. 

Pure Joy

I've often said that Teddy lives in the moment, and he had some very joyful moments last week Thursday. We spent our first night in a hotel in at least 18 months. 

Some kids love hotels for swimming pools, like AJ. Others love the endless selection of shows on TV, like my enjoyment of the Food Network. (OK, most people now have access to so much media that this isn't exciting, but we have never had cable.) Teddy, well, he simply enjoys being someplace different that's not entirely Teddy-proofed.

From the moment he rode into the hotel on his chariot (the luggage rack), he was grinning ear to ear behind his mask. He couldn't contain his joy when we got into the room and immediately ran around exploring everything. He bounced on the bed. He laid on the bed and did his happy feet. He sat on the couch for a millisecond. He discovered there were holes in the wall and insisted that each of us try out each hole to see what we could see. He discovered the bathroom. He discovered the phone. He found the TV remote. 

Teddy loved the windows in the wall. 

He spent at least an hour bouncing around the room. We attempted to settle him for bed around 9, but he chose instead to perch on the air conditioner like a cat staring out the curtain into the parking lot. (He might have dislodged the cover on the air conditioner. Apparently it's not designed for cats the size of Teddy.) 

Teddy was channeling his inner cat.

He finally settled down to sleep by 10:30 p.m. without tears or screaming from any of us. He simply was too excited to lay still. He also stayed asleep until right around 5:45 a.m. For many people, that's insanely early. For Teddy in a hotel room, that's what we'd call a great night's sleep. 

We were both anxious about a hotel stay for multiple reasons, COVID being one of them. The reality is, though, that our biggest concern in hotels is always how Teddy will sleep. We've spent nights trying to get him to sleep until after midnight. We also have routinely been awake before 5 a.m., often on nights that he didn't fall asleep until extremely late. We also had that one morning when he woke up for the day ... at 2:30 ... in the morning. When you spend all your energy fighting him to sleep only to wake up insanely early, it's grueling. 

So in some ways, this was a test of the Teddy travel system. If we had a horrible night's sleep, we would have spent from now until our next trip dreading it because of the sleep struggles. I know one good night's sleep is not a guarantee of peaceful dreams for every night when traveling, but it gives us hope that with his development and the multiple medications intended to help his body rest at night, that vacations might be slightly less stressful.

And that, my friends, is a reason for sweet dreams. 

Mayo Clinic of Genomics

Today was monumental for our family. We visited the Mayo Clinic of Genomics for the first time. We spent 2 hours with a team of 5 people who not only know what Congenital Disorders of Glycosylation (CDG) are but have invested their lives into supporting families and research and development of treatments to improve quality of life.

Two months ago we thought the only CDG clinic in the United States was at Children's Hospital of Philadelphia (CHOP). Given that Teddy is relatively healthy, a consultation and trip there didn't make sense for us. However, at the World CDG Conference, I heard Dr. Eva Morava present and reference Mayo Clinic's work with CDGs. Within a week, we were scheduled for a consultation and asked to join a natural histories research study. (Interestingly enough, last month I learned another PIGN family in Canada is attempting to remotely participate in the same study.)

Mayo Clinic, with a nice mask reflection to remind us that COVID is still a thing.

Although I was excited for today's visit, I was also leery of the first portion because it consisted of an EKG and labs. If you've never had an EKG, it's an entirely painless test that should take literally a minute or two, probably a total of 10 if you count hooking up the wires and the stickers. Let's just say our experience took approximately an hour and required an extra tech because we needed 3 of us restraining Teddy. The removal portion of the wires and stickers was really quick because of all the practice Teddy had ripping them off when we were trying to actually do the test ... by then, he was a pro and ripped off most of them himself (aside from the one sticker that we discovered when we changed him into pajamas tonight).

From there, we headed to labs. They needed probably 10 vials of blood or so, along with a urine sample. For Teddy, that means attaching a plastic bag to catch his urine. That experience wasn't pleasant for Teddy and again required an extra tech because 3 is better than 2 for restraints. My apologies to Teddy because I'm the one who removed his collection bag ... and it was sticky, but oddly he wasn't fazed by that.

Once we got through the torture sessions, we were able to finally eat some breakfast (because they were fasting labs) before we actually saw his team. His team consisted of the nurse, who was only there for vitals, and then the genetic counselor, lead researcher, a resident doing rotations in the clinic, a dietician and a world-renowned CDG expert Dr. Morava. We had to move to a different room to accommodate the entire group because we met with them collectively. That had several advantages in terms of shortening our overall visit time because they collaborated for what they needed and allowed them to multi-task on doing Teddy's evaluation while Dr. Morava talked with us. 

Our visit lasted approximately 2 hours and covered everything from a refresher on Teddy's diagnosis to what's intended with the research study to concrete answers to questions we had, all while examining Teddy. While some people might be overwhelmed by 5 medical professionals in a room, with their genuinely caring personalities (and the fact that they weren't doing any procedures), Teddy instantly became his happy self. He was thoroughly showing off for the team, not necessarily showing tremendous fine and gross motor skills, but did he ever show off his charm! He was giggles, smiles, shenanigans (apparently he wasn't supposed to talk on the phone?), persuasiveness (as he directed exactly what everyone should do and where they should sit) and joy. He was perfectly content with all the attention and particularly enjoyed the fact that none of the team cared when he discovered the sink in the room. I'm not exaggerating when I say he washed his hands for at least 15 minutes straight ... if not longer. And he totally dunked his head under the water, too, so his hair was soaking wet.  

We received a couple educational materials, which is pretty cool to get Caring for Your Child with CDG and A Message for Parents of Children with CDG. Although we haven't had a chance to read them yet, I'm eager to and look forward to the digital versions to share with our other PIGN families. Seriously, to see anything in print on CDG just doesn't happen, so it's a wonderful resource. 

Dr. Morava also walked us through a diagram they're piloting for educational materials. Without her explanations, it's probably Greek to you. With her explanation, it helps us understand better Teddy's specific type of CDG. The more common CDGs like PMM2 affect the sugar blocks at the start of the glycosylation process. GPI-anchor ones like PIGN affect later in the process and prevent the final sugar block from attaching (see the left side of the middle part of the diagram). Since GPI-anchor disorders impact later in the glycosylation process, it is harder and more complicated to develop treatments. 

This is glycosylation. Makes perfect sense, right?

The key things they are working on are a blood test to concretely diagnose GPI-anchor CDGs. Right now, the only way to get the diagnosis is through exome sequencing, which is extremely expensive, time consuming and only provides the "likely pathogenic" mutations. In other words, it's not a confirmed diagnosis with a concrete test. They're working on a simple blood test that would allow correct diagnosis sooner, cheaper and more effectively. Also, that blood test would confirm that the PIGN mutations are pathogenic, that there's a GPI-anchor disorder.

That confirmation will pave the way for gene therapy. Gene therapy treatment is not in the immediate future, although she predicts it will be approved in about 3 years. That approval is not necessarily for CDGs, but once gene therapy starts getting approval, it will be relatively simple (her words, not mine) to transfer that knowledge to other genes. I'm extremely curious on what potential gene therapy might have for older individuals, but I didn't ask the question because the treatment isn't even developed yet.

But the exciting thing about working with this team is that we'll learn all these things. We'll know when there's new developments, what's happening in research and be a part of that. They look to collaborate with parents to make sure the materials make sense and that the work aligns with the needs. In fact, she mentioned the possibility of getting someone to research why CDGs present so differently in different people, the wide range of impact and the differences even among family members. That would be fascinating.

One of the things we asked about was the COVID vaccine because we've heard different things on how COVID and the vaccine may impact people with CDGs. Dr. Morava shared that they have patients with CDG who have been vaccinated and then evaluated for the effectiveness. She said that because of how CDGs impact immune systems that the vaccine is less effective. However, she said that GPI-anchor disorders are less impacted than other CDGs in terms of the immune system, so the vaccine should be more effective for a PIGN person than a PMM2 person. She still recommended the vaccine as it provides some protection but cautioned that it won't provide the same effectiveness level as the general population. This was good for us to hear as it means we'll want to ensure Teddy gets the most effective vaccine available, knowing that he won't get full effectiveness from it. 

I know this is a lot of information, some far more technical than usual, but I want to share it for other CDG families as well as for our own future reference.

The team was absolutely phenomenal. They genuinely were excited to spend time with Teddy and were absolutely fantastic with him. My mind is boggled by the incredible intelligence of Dr. Morava, yet the humility and ability to connect with both us and Teddy. (Teddy generally disregards COVID precautions, so he was hugging her while chewing on his mask.) I'm even more amazed that Dr. Morava is Hungarian, spent time working in the Netherlands and then was recruited by Mayo. How you can pronounce all these technical terms in one language, much less at least 3, is beyond my comprehension. Heck, I was just impressed that I can count to 10 in German after nearly a year of Duolingo ...

Oh, fun fact, the researcher is actually from Germany! I'm pretty sure that of the 5 people on Teddy's team, at least 3 of them were born in other countries. I'm so excited to have such a great team for Teddy to partner with his neurologist. We'll be scheduled to go back in a year for the study and follow up, but we now have a terrific resource where we can reach out should we have any questions or concerns.

Now, I just need to remember to share with ya'll in another post the excitement Teddy had about our hotel stay leading up to his appointments. 

CDG World Conference: CDG Basics

This year the World CDG (Congenital Disorders of Glycosylation) Conference was hosted entirely virtually, which enabled me to attend and even participate as a panelist for a session. This event typically rotates between San Diego and somewhere in Europe, every other year. That travel component and cost has been the primary reason I haven't attend in prior years. After my experience this year, I might need to invest in plane tickets in the future. 

The conference was 4 days, which is mighty long for a virtual conference with back-to-back 6- to 8-hour zoom meetings. However, it was well worth the screen time. There were a variety of sessions, some more valuable to me than others.

One of the most useful to me was essentially CDGs 101, an introduction and overview to the variety of CDGs. Here's a few of the most interesting things I learned or relearned:

1. The first CDG was discovered in 1980 by Professor Jaak Jaeken. In fact, World CDG Day is celebrated on May 16 in honor of Professor Jaeken's birthday. Although he turned 80 this year, he is still one of the most active and prominent advocates for CDGs. 
2. The first CDG discovered was PMM2, which is also the most common CDG, not surprisingly. In 2009, there were approximately 40 known types of CDG. Now in 2021, there are 161 known types with more added each year. Teddy's PIGN-CDG was first discovered and documented in research in 2011.
3. All CDGs are metabolic disorders that affect how glycans (sugar-building blocks) attach within the cellular level. There are different pathways that are affected by different CDGs. The conference shared that currently there are known to be 3 types that are lipid linked, 27 GPI-anchor, 34 that are N linked, 46 that O-linked and 56 that are multiple pathways. I wish I could you specifically which type PIGN-CDG is with certainty, but honestly I'm not certain. I am confident it's GPI-anchor, but it may actually be multi-system with one of those being GPI. If you figure this out, let me know.
4. CDG affecting the same gene can result in multiple diseases or presentations of disease. To some extend, that's why we see such dramatic differences in the functioning level of our PIGN children.

I will work to share additional thoughts on the conference in the future, but I don't care to bore you with all the fascinating things all at once. 

Professor Jaeken still advocates for the CDG community at the spry age of 80.

What a Week!

I know I shared a post about a morning in my life the other year. I'm not going to lie. I'm mildly exhausted just re-reading that. I thought I'd share the highlights of last week, simply because it was a doozy.

Monday
Monday was a Monday in the truest sense of the word. Dave said, though, that Monday morning put his entire week into perspective because, well, it couldn't be as bad as Monday morning. I was just about to take a shower when Dave informed me that he needed "a little help."

Let's say Dave and I have different ideas of what "a little help" means. In this case, it meant Teddy had removed his diaper, discovered homemade brown play-dough (as someone else said almost making me spit out my food laughing) and smeared poop into his carpet, all around his door handle and on his body. Even better was when I stepped in the room, and Dave warned me to be careful because there was poop everywhere including the door knob I had just touched. Just a bit late with that warning.

I'm grateful Dave was there to discover the mess. He showered again ... with Teddy ... while I scrubbed and sanitized the room. And then I showered, but a shower doesn't quite fix that.

Oh, and Monday was also the day we learned we didn't have staff, so I had to leave work early to be home when Teddy arrived home. On the bright side, that gave me time to work on multiple loads of laundry that I had to do for some reason.

Tuesday
I feel like Tuesday was uneventful. Maybe I'm blocking what happened from my memories, but I'm pretty sure I'd repress Monday instead of Tuesday.

Wednesday
We learned that Teddy will be featured in a research paper/presentation at a genetics conference in March! Someone had reached out several months ago, inquired if we'd be interested, and we supplied a bunch of information. Her proposal was accepted, so she informed us and requested photos to use.

We're super excited that there will be updated information on CDG-PIGN because there's so much more positive than what the original research shows. Any research can help to raise awareness, and we've only been waiting since Teddy was diagnosed in 2015 to get him into research. Our genetics team went through some changes and is incredibly backlogged ... as in I'm not sure it'll ever happen.

Thursday
Remember how Teddy's doorknob got covered in crap earlier in the week? That meant I threw out the child safety lock because it was packed with poop. On Thursday night, AJ ran downstairs to grab something for me right before bed. I locked Teddy's door from the outside to keep Teddy from following AJ, knowing that AJ would be right back to unlock the door. AJ returned, we read stories and then AJ discovered he locked us all inside Teddy's bedroom accidentally when he returned.

Some of the first words out of my mouth, "You better make yourself comfortable. We're going to be here a while."

I am not good with door knobs. I can manage, but I don't like to take them apart, fix them, etc. I had no phone to call for help. Dave was gone for several hours yet. I didn't even have a phone to Google guidance. But I did have a screwdriver and sheer determination to get out of that room and get those kids to sleep. I succeeded with only minor tears from AJ and almost me.

Friday
Kids are at school. I have the chance to catch up on a few things, including finishing a sewing project. I made a weighted blanket for one of the other families whose son has CDG-PIGN. Actually, both their sons have the disorder. But one of the boys struggles to settle to sleep, similar to Teddy. (I joke with this mom that she's living my future life, so she can win the lottery any day now, so my day would be coming in 10 years.) She had mentioned wanting to try a weighted blanket for him, so I made one since I have the supplies on hand. I can't do everything for our PIGN families, but it fills my bucket to help any of them in any way I can. It's not an easy path we're on, but it's so much easier to have others who walk the path with us, ahead of us and behind us.

Saturday
It was a long 6 hours in a car to get to and from our niece and nephew's fun birthday party ... plus chasing Teddy there. So to relax we settled down to paint our entire kitchen and living room ceilings. Wait, that's not relaxing, but it's a project that's been years in the making, so it was on the docket for the weekend. When Dave went to the store to get better supplies (as in a ladder instead of a rickety chair that would be the death of one of us, leaving only one of us to finish all the work and raise the children), I determined the thumping sound upstairs was Teddy still awake. I discovered this when checking on him:

His room wasn't possessed by ghosts, but he had wiggled under his fitted sheet. He hadn't ripped off a corner to crawl under, just wiggled inside. I determined I should pull him out to avoid suffocation through the night, which then necessitated laying by him until he fell asleep. I might have told him that was way better than painting the #$%# ceiling.

Sunday
We finished the ceiling. All rested, relaxed and ready to start another week. Well, let's just say another week is starting even if that's the only true part of that sentence.