NIH Natural Histories Study - Day 3

Dave drew the short straw when he volunteered agreed do the sleep study with Teddy. Dave is much better at putting Teddy to sleep than I am. My tactics include giving up easily, going for vehicle rides and crying. Dave somehow actually gets him to sleep. I think he has this thing called patience, which was needed last night.

Teddy fell asleep around 9 and slept until midnight or so when they tried to do the metabolic cart. That is apparently where they put a hood over Teddy to record how much carbon dioxide he’s exhaling. That indicates how efficiently his body metabolizes sugars. That woke up Teddy and freaked the bejezus out of him, which resulted in screaming for 1.5 hours before Dave’s magic worked to get him back to sleep. He woke up again around 5, making weird sounds and having gasses exit his body all at once. That freaked Dave out because it looked abnormal enough to look like possible seizure activity. The nurse came in but didn’t witness any of it, but anything should be captured on the EEG.

I'd freak out, too, if I woke up with this on my head.

I headed over from the Children’s Inn as soon as Dave text that he was acting weird, then returned to the Inn to grab some breakfast for us for later and returned to sit by Teddy while Dave tried to relax. Teddy woke up by 6:15 and was done with the sleep study. He was still exhausted, but we knew he wouldn’t be going back to sleep. He cried while he was unhooked from everything, but he managed a few tired smiles from behind his pacifier as he left.

We went back to his room, and I paced the halls with him in his chair, pushing his IV pole. We played in the playroom a bit, keeping him in his chair to prevent him from wrecking his IV or falling over from exhaustion. He did a few weird burps and spit up clear liquids, mostly stomach bile from the smell on my hand. No idea why that happened, but that has us a bit concerned about him. We’ve stressed his body an awful lot this week, and he’s beyond exhausted, both of which make seizure activity more likely. He was still able to get his sedated procedures, which is where he is as I write this portion.

He's being sedated for an MRI, lumbar puncture, skin biopsy, dental exam, hearing exam, eye exam and two different tests that measure nerve and muscle responses using electrical current. All things he wouldn’t tolerate awake, hence the sedation. I held him as he was sedated, which he didn’t like despite the very nice team of smiling people there to help. I’m hoping he wakes up feeling more rested and happier, but I’m not expecting that to be the case because of both the sedation and the procedures.

We met with Dr. Carlos Ferreira, the doctor in charge of the study. He spent about 45 minutes with us, discussing CDGs and Teddy’s more specific diagnosis. That was extremely helpful because that man is incredibly intelligent and explains things in a way that makes sense. He is also compassionate, as evidenced by him undergoing a skin biopsy to know what it is like for those participants in the study. We learned quite a bit from him. He said there’s more than 8,000 rare disorders, and there’s no gene therapy for 7,900+ of them. The goal for now is to treat the symptoms, which he said Teddy’s therapy and Keppra are doing well.

He spent some time explaining the diagnosis and said he wouldn’t call Teddy Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 1 (MCAHSS1) because Teddy doesn’t fit the clinical diagnosis. He has the seizures and the hypotonia and the developmental delays but not multiple congenital anomalies. Dr. Ferreira explained that the medical community is divided into lumpers or splitters (his words, not mine) who either lump groups of disorders together or name each one individually. Apparently, the doctor who discovered CDGs in Belgium is now advocating that CDGs be classified as the gene name – CDG. So Dr. Ferreiera would call Teddy’s diagnosis either PIGN-CDG or GPI-BD3. The GPI-BD3 refers to the GPI-anchor aspect where sugars aren’t processed/attached as they should, and quite frankly I don’t remember what the second half means. I didn’t have the heart to tell him that I couldn’t remember or pronounce all those words, so I didn’t think it was a good idea to change Teddy’s diagnosis. Basically, what he’s getting at is that it’s all semantics, but the words used to diagnose Teddy aren’t reflective of Teddy’s medical symptoms.

He also spent some time explaining alternatives in the event we were interested in pursuing another child (ha, not unless God has a wicked sense of humor). He explained the logic, though, as a way to think of AJ potentially having children affected. There’s a 2/3 chance that AJ is a carrier of this recessive genetic mutation. But the odds of him finding another carrier are less than 1%. That does mean the odds of Dave and I finding each other were way less than 1%. How come we’ve never won the lotto?

The time with Dr. Ferriera was very informative. He confirmed my belief that right now the only way to accurately diagnose this disorder is with the exome sequencing or the specific analysis of the PIGN gene, which is why the testing of that specific gene in a newborn could produce results in 2-4 weeks instead of 3-6 months for exome sequencing. There are blood tests that look at how GPI anchors affect proteins that could indicate a GPI-anchor disorder but not which specific one. And if you think I understand what GPI anchor means just because I’ve written it a bunch of times, you’re wrong. Google it. And then feel free to explain it again to me next week.

This model shows why they perhaps have an escort service. It's a huge place.

The other appointment we had while Teddy was sedated was with a genetic counselor. Dave joked (only partially) afterward that he didn’t realize it was a counseling session, not a genetic counseling session. She took Teddy’s history and our family history but spent much of the time asking questions about how we handled the initial diagnosis and the years since. That was a bit different than what we anticipated, but she was genuinely interested and compassionate. I think the information we provided helps with better presentation of information to other parents in the long run. We did discuss whether the specific mutations we gave to Teddy alter the impact of the disorder. The general thinking is that yes, the specific mutations affect how the disorder presents, but there’s nothing more really known. It seems like each person has what is called private changes, meaning that Teddy’s mutations are all his own and not the same mutation that shows up in someone else. The splice site mutation he gets from me can change the gene more dramatically, which could either minimize the impact or be more damaging to the gene. There’s not enough known, but the specific mutations are part of the research they’ll be doing.

We’ve also heard from both Dr. Ferriera and the genetic counselor about a variation in Teddy’s SCN1A gene, which is a gene associated with seizures. This gene was tested before his exome sequencing, but the variation he has is one that Dave or I have as well (as best as we remember). That’s why it was determined to be a mutation of unknown significance, meaning it’s not likely the cause of his seizures since that mutation doesn’t cause Dave or I (whichever has it) to shake, rattle and roll.

The other impressive thing, to me at least, is the appreciation shown by Dr. Ferriera, the genetic counselor and the other team members in our willingness to have Teddy participate in this study. They are very understanding of how stressful the week is and that parents usually don’t love them at this point in the week. We know this week is incredibly tough on Teddy, but we also feel like we’re getting the chance to talk to experts for the first time. It’s worth it for us and for the future of CDGs, especially those with PIGN mutations.

Those appointments kept us distracted from Teddy’s sedation, but the 1.5 hours waiting after them left us both antsy. However, they allowed both us back by Teddy as he was waking up more, which was nice not to have to pick one person. The anesthesia left him wobbly all afternoon, much like the Jello boy he was after a previous MRI. His mood improved as more of the medication left his body, although he still wanted full freedom from his IV of fluids. (The fluids help him regrow his spinal fluid and help with a spinal headache, in the unlikely event he develops one.)

We met with immunology in Teddy’s room about an hour or so after we got back there. That meeting was relatively brief as Teddy was still waking up and required more attention. We discussed possible allergies and opted not to do additional allergy labs because he’s already been stuck so much this week. There’s some concern for a possible dust or mold allergy irritating his eyes that might be why he rubs his eyes so much in the evening, as opposed to being tired as we assumed. The plan, as I understand it, is to put him on a regular course of Zyrtec to see if that changes his eye-rubbing behavior. We should know more once all the sedated procedures and test reports come back. The other interesting piece shared by the immunologist is that some of the CDG patients actually show improved responses to vaccinations, which is an area of further study to see if vaccines could potentially be improved to be more effective for the general population.

This is why we're doing this study. Teddy is making the world a better place.

 

We worked to entertain Teddy until his nutrition visit while keeping him contained in his chair because his couldn’t or wouldn’t bear weight on his legs. He ate a banana and had just started on his milkshake when the nutritionist walked in the door. (Timing is everything, right?) The nutritionist also misunderstood me and thought Teddy was drinking 5 milkshakes a day here. Sheesh, that’s a bit extreme, even for my child. We learned from the nutritionist that Teddy’s Vitamin D levels were excellent, which is apparently really rare in children (especially those from Wisconsin in winter, I’m sure). The only other finding she noted was slightly low iron levels, so she recommended switching from gummi vitamins to a chewable one that contains iron.

Based on our discussion, she recommended some adjustments, such as limiting Teddy to 3 cups of milk a day (which is pretty normal, although he sometimes has more) and eliminating apple juice since he eats a good amount of fruit. We discussed ways to possibly get him to eat vegetables since the only one he'll eat is potato in the form of a French fry or possibly tator tot. I would imagine most parents would feel the same as I do in talking to a nutritionist that there’s room for improvement in helping their child eat better. Still, in the grand scheme of life, finding a way to get Teddy to eat vegetables has not been my top priority. She mentioned that it appears Teddy is increasing percentages and suggested discussing with his PT whether his increase in weight impacts any of his potential gains. Part of me wants to roll my eyes because I think Teddy’s actually become more lean through the past year and looks well proportioned to me. The other part of me recognized that with as much input we have into Teddy’s eating habits, there’s plenty of opportunities to try to make some better habits. (I do think I got brownie points … errr, carrot points … for making waffles and pancakes from scratch. At first she thought homemade waffles meant from a box mix, which she still was giving me credit for doing.) 

 

That was our last appointment of the day, so we waited impatiently for Teddy to be disconnected from IV fluids. He still has the IV yet tonight in case he were to develop a spinal headache or have any issues from the anesthesia this morning. He should be able to get it pulled tomorrow as soon as his nurse has the time when we have a break in his schedule. Teddy was really happy to see Lynne and was his normal self (albeit sitting in his chair) with her and Tara. Teddy even convinced Tara to play peek-a-boo with him by hiding under his blanket and got her to put his medical chart stickers on his nose and took all the extra copies of his schedule from her and then handed her back a nicely drooled one. In other words, Teddy was Teddy. Lynne said all went well today, although results aren’t back yet from all the tests.

She reviewed tomorrow, which starts with a swallow study and is mostly play-based evaluation through the middle of the day ending with one more non-invasive procedure. We explained that we’re hoping to leave tomorrow evening as soon as we’re done to head halfway to meet a family from Philadelphia who got their diagnosis of MCAHSS Monday of this week. We remember all too well the overwhelming emotions, questions and fears that come along with the diagnosis. Dave was actually the one who suggested offering to meet if they were available to meet somewhere in the middle. That’s the plan, so we’ll hopefully pull it off tomorrow evening without too terrible of traffic or other issues.

After we escaped from the clinic, we attempted a partial wash of Teddy’s hair using a towel to get rid of some of the gunk from the EEG. At least he smells like shampoo now instead of chemicals. Dinner at the Children’s Inn tonight was a fantastic potluck put together by one of the clinical teams. There was an incredible assortment of food ranging from fried chicken to dinosaur chicken nuggets to macaroni and cheese to quiche to meatballs rounded out with a few more casseroles, vegetables and fruit. There was a table of desserts, including a cookie-decorating station for the children. It might have been extra delicious because lunch today consisted of trail mix and a chocolate milk I stole from Teddy, but it was so nice to see such generosity. They even had tablecloths and balloons as table decorations!

Oh, I know this is incredibly long already, but I learned there are 7 branches of uniformed service. I asked someone today about her attire because there's a handful of folks here wearing weird outfits with stars on them. I had no idea there was a United States Public Health Service Commissioned Corps. But there is. And they protect America on the healthcare front. There's also National Oceanic and Atmospheric Administration Commissioned Officer Corps., which protects America from bad weather. Wait, I'm making up their mission, but not their name. Definitely learned something new today.

Teddy is snoozing comfortably (for now at least and hopefully all night). Dave is listening to one of his classes in the common areas. And I’m about to retrieve our laundry, fold it and work toward an early bed.