The Smiling Faces of PIGN-CDG

Happy World CDG Day! 

Nine years ago I did the first of these World CDG Day posts, celebrating and sharing our rare community. It amazes me to look back and see only 10 families from 4 different countries when we now know of slightly more than 100 families from more countries than I can list. 

A quick bit of perspective (and shameless fundraising plug) is that 100 families around the entire world does not gain any traction in the pharmaceutical field for treatment. What hasn't changed in the past 9 years is there is still no known treatment for PIGN-CDG, so families are left treating individual symptoms like seizures and still receive a pretty bleak prognosis. We're working to actively change that (and have some promising initial results) through our parent-led drug-repurposing initiative. You can learn more about that (and donate if you choose) here.

In honor of World CDG Day, I want to introduce you to our rare, wonderful children (and now adults!). It is my honor to share these beautiful souls with you, most in their parent's own words. Though it's bittersweet each year to see those who are no longer here with us. 

Australia

Brianna, age 22, and Zachary, age 17

Brianna is a happy, cheeky young lady who loves music, sunshine and Peppa Pig. She loves going on train rides especially if there is a stop to grab a milkshake. Her giggles are as bright as the sunshine.

Zachary is a bundle of smiles and a ray of sunshine. He loves being around people and joining in every activity where he can. He also loves music,and you can always count on him to help out if you ever need a hand.

Zachary and Brianna are siblings who share a love of life!

Daisy, age 10

Daisy loves her independence, including helping herself to food from the fridge. Daisy loves all kinds of music, but her current favourites include Taylor Swift, Kasey Musgraves and her nana’s Rock 'n roll. 

Daisy enjoys surfing and went viral at a Taylor Swift concert!

Brazil

Rael, age 1 year

Rael is the happiest boy in the world. Sweet and adorable, he has an incredible will to live. He goes to therapy every day, and all the staff absolutely love him. He loves the beach, the pool, and being out in the sun. His canine siblings are his favorite playmates. Oh, and he absolutely loves eating and traveling! So many people follow his journey and are inspired by his strength!

How can  you not love Rael's sweet smile!?!

Canada

Isabel, age 34

Isabel loves life!  Each day she wakes up smiling, looking forward to what excitement the day will bring.  She likes to use her iPad to talk, to read, to make art, and to look at photos of her favourite people, animals, and Beanies.  Isabel loves to draw and make music.  Her favourite instrument is the drums.  She is an avid Beanie collector, and Isabel loves to shop for these, and to meet new people.  

Isabel is such a fun young lady!

France

Alliya, age 18

Passionate about music, Alliya loves watching music videos with her headphones, following the show Familles nombreuses on TV, and dancing. That’s why she joined an inclusive Zumba association, where she receives personalized support to learn choreographies. She also enjoys spending time with her little brother and, most of all, going out with her family.

A true foodie, she never says no to a McDonald’s meal or a restaurant outing. But what she loves the most is traveling by plane and enjoying vacations by the sea—moments that bring her immense joy.

Alliya loves zumba and vacations!

Hugo, age 5

Although Hugo does not walk or speak, he is a super happy boy. He had gastrostomy last year that changed his life, and he can still enjoy food during the day. It is a beautiful adventure to live with Hugo, and every step we take together is a success.

Hugo is a happy boy with his family!

Germany

Anna, age 7

Anna is a happy girl and the best big sister. She loves music, dancing and swimming and pizza. She loves to be together with her family. She also likes being at school and going by the school bus. She has the most precious smile. 

Anna is such a fun, sweet girl (who my Mom and I got to meet in Germany)!

Lotta, age 15

Lotta loves to go to school and meet her friends there. She loves drawing and cooking. She walks a lot together with her family and dog and is sometimes bored of her parents.

Lotta is a beautiful, creative young lady!

Hong Kong

Annabelle, age 4

Annabelle has an infectious smile and loves to hug people. Her special power is making anyone feel special (aww she must like me) as she would hug anyone … literally. She loves going to school (kindergarten) and claps to music. 

Can't you hear Annabelle's laughter from this adorable picture?

Italy

Joele, age 3

Joele loves playing, being with children, being outdoors and is always smiling.

Joele loves fresh air!

Marco, age 4

Marco is a sunny child, always smiling and stubborn about the things that interest him. He loves being with his friends and is loved by everyone.

Marco is social and loves to make guest appearances on our PIGN zoom calls.

Margherita, 9

Margherita is the sweetheart of the family. Her character is beautiful, and she is sunshine on cloudy days.

This sweet girl lives with her sister Matilde.

Matilde, 14

Matilde is a beautiful teenager. She has immense inner strength despite having a weak physique. 

Matilde paves the way for her younger sister Margherita.

Korea

Jooyuri, age 2

Yuri is a toddler with a lot of laughter. She likes to hug her grandfather the most and play with the dog. Yuri is a toddler who always smiles brightly. She is a charming friend with a dimple. 

Yuri is such a sweet girl!

Northern Ireland

Amelia, age 3

Amelia is social child who loves been around people. Amelia loves Bluey and her sensory toys and being around the people that love her. 

This sweet girl keeps her mum on her toes!

Charlie, age 5

Charlie is Amelia's older brother. This happy boy seems to need no sleep to function, just like his sister, but not like his poor mum.

Charlie is such an adorable lad!

Chloe, age 5

Chloe is a happy, loving child and is very social. She loves having fun, dancing, music (especially Abba), art, shopping and playing with her friends at school. She also loves to help out at home, especially with her baby sister, Phoebe.

Chloe has great taste in music!

Poland

Antoni, age 15

Despite his disability, Antoni is a joyful teenager who loves the world and people.

Antoni is a handsome young man!

Emily, age 14 

Emi hates wearing socks and loves her bare feet. She's a big sister who loves her brother!

Emily's mom founded our PIGN group and is a great advocate!

Kinga, age 17

Kinga loves to play with other children, enjoys baths and playing on trampolines.

Kinga is a beautiful young lady!

Konrad, age 3

Konrad is a joyful child, and he likes to eat a lot. Konrad loves to play with toys, and he enjoys life.

Konrad loves to play like every other toddler!

Zuzia, age 7

Isn't Zuzia adorable?

Qatar

Olivia, age 7

Oliva is a happy girl who loves socializing. Even though she is non-verbal, she finds a way to express herself with giggles or eye contact that makes her absolutely adorable. She's a fan of music and dancing!

This little lady loves to dance!

Saudi Arabia

Abdullah, age 4

Abdullah is a child who has been in the hospital since birth and has never seen the outside world. He is a calm child, but he is not aware of his surroundings and his condition is relatively stable.

Abdullah is a sweet, calm boy.

Spain

Claudia, age 6

Claudia loves playing in the water and enjoys being around animals. Her favorite thing is coloring. 

Claudia is an artist!

United States

Adeline, age 7

She loves to ride her horses, she has loved her swimming therapy and can now read her name! 🙂

Adeline is active with swim therapy and horse riding!

Alexa, age 12

Alexa is the life of the party. She loves to be around people. For her, the more noise and excitement, the better. She also loves to chew on anything and everything she can get her hands on, to a fault. She’s full of spunk, sassiness, and smiles. 

Alexa is all sugar and spice! She's a doll who we've been lucky to meet twice.

Alice, age 6

Alice loves a good laugh and usually gets one when she sees objects thrown in the air or fall onto the ground, when she’s tickled, or when she’s watching Bluey or Blippi and Meekah. She used to be a big foodie until she switched to a g-tube diet for her safety. She still misses her old foods, but hopefully, with feeding therapy she’ll be able to have them again one day. She loves being around her younger brother and going to school.

Alice is all smiles! Her parents are tremendous advocates, leading the drug-repurposing project!

Aniyah, age 10

Aniyah has a smile that lights up any room. Despite everything she has been through, she still smiles.

That smiles reaches beyond any words!

Camilia, age 8

Mimi loves makeup and playing with her dolls. She loves music and being creative. 

Mimi has style and smiles!

Charlotte, age 1

Lotte is a little ball of sunshine. She's 1.5 years old, and she absolutely loves her big brother, her puppy, and her kitty (and they love her). She spends her days playing with her rattling toys and watching big brother run around the house like a crazy person.

Lotte loves her big brother!

Gianna, age 9 months

At just 9 months old, Gianna is a shining example of strength and spirit. Despite all the challenges, she remains strong and is her family's little warrior. Gianna loves to hear the sound of familiar voices and enjoys when they read to her. 

Gianna loves her family and enjoys listening to books!

Hayden, age 4

Hayden is the sweetest little boy with a smile that can brighten any room and a laugh that brings joy to all who hear it. He loves listening to music and going for walks. This year, he has been riding the bus to preschool and gets so excited when he hears the words "school" or "bus" or "friends"!

Hayden love school and his friends! He's a sweet dude who we met in person!

Hazel, age 4

Hazel is always so full of joy. She loves meeting new people, but you will always know who her favorites are. She loves music of all kinds. Pink and purple are her favorite colors. One of her many strengths is being able to use sign language to communicate with people. 

Hazel shares her joy with others!

Holly, age 2

Holly is Alexa's big sister. Holly was a fighter who passed away when she was 2 years, 4 months. Holly always had a smile when her mom was nearby.

Holly was full of smiles when she was near mom!

Jacob, age 3

Look at that smile!

Julia, age 8

Julia loves riding her horse, Peppa Pig and her family!

Julia loves Peppa Pig!

Konrad, age 6

Konrad is always smiling and happy, and his smile makes everyone feel better. His smile is contagious.. He is full of energy and very active and loves to play with his siblings. He also loves  his toy piano and various toys that he can bite on. Konrad only when he is hungry he can be cranky-he always has a good appetite and loves home-cooked food. 

Konrad is active and loves home-cooked meals!

Levi, age 4

Levi is mostly non-verbal, but he occasionally says a word. He is able to walk, though he's unsteady. He attends preschool.

Levi brings joy wherever he goes!

Maddison, angel at age 9

Maddison was a happy girl. Her smiled lit up a room. She was also very onery!! She loved being outside on her swing no matter the weather.  She also loved being around her family and siblings. She is our angel girl!

Maddy lived her best life with her loving family!

Nicholas, age 8

Nicholas is our little ray of sunshine, a blessing to us from God! He loves listening to all different types of music, is a wonderful, easy going, fun-loving boy, who’s in the 2nd grade! He enjoys playing with his little sister, cuddling/snuggling with his mom, babbling with his dad and adores his grandma who cares for him while his parents work. 

Nicholas has  a special relationship with his grandma!

Ryan, age 20, and Zach, age 23

Zach and Ryan love traveling, being outdoors and music! They are usually joyful and ready for adventures. 

Ryan and Zach are travel buddies who love cruises with their family!

Sammie, age 18

Sammie lives life with so much joy and love. She is very social and loves going to school, shopping at the mall and participating in activities with her friends. She loves music and has recently discovered the excitement of going to a concert (specifically Taylor Swift!).

Sammie is a social butterfly who loves music!

Sebastian, age 5

Sebastian is the sweetest kid in the world. He loves dogs, water and nature. He also loves to play with all types of strings. He is a warrior and super affectionate!

Sebastian is all smiles and affection!

Taytum, age 5

Taytum is the sassiest, most social, and loving little girl. She loves music, baby dolls, and spending time with her favorite people! Her perfect day would include riding around on golf carts, tricycles, truck rides with dad, eating a grilled cheese and Reese, and playing with her big brother.  She makes life so fun!

Taytum is the perfect blend of sassy and sweet!

Teddy, age 11

Teddy is a happy, social boy who loves to be around people - he literally jumps for joy when he sees his favorite people! Teddy loves trains, buses and especially tractors and often spends his summers driving tractor with his dad and grandpa. Teddy loves being in middle school, especially all his friends and his teen life class where he bakes and cooks (and then eats!).

Teddy's smile makes up for his shenanigans ... most of the time!

Zayir, age 4 months

Zayir taught us so much about patience, faith, and love. He has so many love to give with his siblings and parents. Zayir is a warrior since the day he born! 

Zayir is a little fighter!

Rare Disease Day: 2024

Rare Disease Day is always celebrated the last day in February, and it feels extra special when it falls on February 29 because that's extra rare. It's a day to focus on rare diseases and raise awareness of them. 

One of the common sayings you'll hear is Show Your Stripes. The reason is that often the medical community thinks of the most common diagnosis just as people most often think of a horse when they hear hoofbeats, for example. The challenge is to consider rare explanations as well, such as a zebra (or in Teddy's case PIGN-CDG).  This year, I was on top of my game and created these little key chain cards to share with Teddy's team and classmates at school to raise awareness. 

Another PIGN mom gave me the idea for these key chains. 

I time traveled this week, reading this blog post from 8 years ago in 2016:  Teddy's Triumphs and Trials: Rare Disease Day (teddystriumphs.blogspot.com) This was 3 months after we first learned Teddy's diagnosis. In the past 8 years, so much has changed. To name a few of the most significant:

1. Teddy's diagnosis is now PIGN-CDG, a more encompassing and accurate description than his original diagnosis of Multiple Congenital Anomalies-Hypotonia Seizure Syndrome 1 (MCAHSS1 for short because that's still not a mouthful.)
2. Instead of knowing less than 5 families with this diagnosis and being the supposed 15th in the world, our .community has grown to closer to 100 with the diagnosis and their families. 
3. Teddy is now 10 and capable of doing so much more than we could have imagined 8 years ago. Not to mention, he's thriving and has made an outright mockery of the life expectancy (3 years) given in the first medical research papers. 
4. An Internet search of PIGN-CDG now yields 6,360 results instead of 3 for MCAHSS1 in 2016. Seriously, that blew my mind that Google didn't have results for our son's diagnosis. 

Yet one significant thing has not changed: 8 years later, and there's still no treatment for this disorder. AJ does a great job explaining this in this Facebook post. (For whatever reason I couldn't get the video directly into this post.) If you'd like to support AJ's in fundraising for PIGN-CDG research, you can place your fidget order here.

This fundraising is so important because research is expensive. While there's much interest (and therefore money) dedicated to researching treatments for wide-reaching disorders and diseases, there's not much interest and money in researching treatments for a diagnosis that affects approximately 100 known people. 

But trust me, the effect this disorder has on those families (and their families, friends and communities) is far reaching. It's an honest statement to say Teddy's diagnosis has impacted every single aspect of our lives. Some of those impacts have been beyond positive: friendships forged, connections created and memories to last a lifetime. Others have been beyond challenging: sorrows shared as we lose children with PIGN (2 within a week of each other this month), trauma from seizures and sicknesses, endless appointments and therapy, elopements and other scares. 

For each of us impacted by this disorder, we care deeply about a treatment. We want to change the fact that we grieve the losses of our children every year. We want less hospital stays and better quality of life for all. Honestly, we want to sleep at night without fearing our children won't wake up in the morning. We want hope, not only for our children, but for those who have yet to receive this life-changing diagnosis.

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.