Month Full of Dr. Visits

Annalise and Bryce each have their own way of entertaining themselves while waiting for the doctors.  These pictures were taken while we were waiting for the Physical Medicine doctor.  Annalise had fun creating a puzzle with the blocks and Bryce had fun trying to kick over the bucket that held the blocks that Annalise was playing with.  He would kick it over and over and just thought it was the funniest thing. 

This is part of the mural that is going up on the walls of the new CRS building in Phoenix.  Annalise picked out this hot air balloon with Mickey on it right away.   They both love anything Disney.

Bryce and Annalise have had a very busy month.  In this month alone, Annalise has had 7 scheduled appointments and Bryce has had 3.   Unfortunately a couple of these appointments have led to other appointments being scheduled.

At every appointment that Annalise has had, she asked if the doctor was going to look in her ear.  Ever since her horrible ordeal in November, she is scared to death of having anyone look in her ears, for fear that it is going to cause a lot of pain.

One of these appointments was with the gastroenterologist.  There we found that Annalise had lost a couple of ounces and Bryce had gained a couple of ounces.  She now weighs 30 pounds and he weighs just over 40.  I wasn't surprised that Annalise had lost a little bit since she was so sick last November and really didn't eat much for about 3 weeks.  I was actually very glad that she had not lost more considering I have recently stopped using the pediasure they have had her on for so long now.  We are really trying to feed her more of the diet that I give Bryce since that seems to be helping him so much.  She is still eating by mouth and loves the taste of all things sweet so it is a little more tricky than it is with Bryce, but getting rid of two cans of chemical sugar water a day should help some.

Dr. McOmber scheduled a swallow study for Annalise just to check and make sure that she is still not aspirating food when she eats.  It has been pretty routine for her, every 6 months, over the last couple of years just as a precaution since eating/drinking has become more difficult for her as she fatigues easily.  Her studies have all been normal and I haven't noticed any new difficulties for her, so I figured this one would be the same.  It wasn't quite.

Annalise did a great job.  She sat up in the chair and ate all the cherry flavored barium food and drink they gave her...even asking if she could take the rest of the cookie with her.  Gross!  Okay, whatever.  She enjoyed watching herself swallow on the x-ray screen.  It was very different than Bryce's ever were.  He is always scared to death of all of it and cries through the entire study.  I always dreaded them, so it was nice that Annalise seemed to thoroughly enjoy herself.  Anyway, luckily there were no signs of aspiration, but this time around they did see a fair amount of penetration going on, which is basically when food or liquid does go into the trachea but stays above the vocal cords and then eventually (hopefully) moves to the correct place.  We will see what the doctor has to say about all of that this coming week. 

 This is the marble wall at PCH Mesa Campus.  Annalise had fun trying to count all the marbles.  I asked her how many she thought were there and she said, "ummm, maybe 30 teen!"

As for Bryce, our neurologist is concerned about the number of apnea episodes that he has been having and is wondering if possibly he is having some reflux that may be causing them.  We talked this over with Dr. McOmber and he agreed that this could be a possibility.  He is going to do a procedure that will measure the amount of reflux that is occurring in Bryce during a 48 hour period.  Since he will need to put him under to do this and since we had an appointment scheduled the following week with the pulmonologist , Dr. M decided to wait until that appointment to see if Dr. Woodward needed to check anything that would require anesthesia. The fewer times he has to be put under, the better.  Dr. Woodward does not, so we should be hearing from Dr. M's office soon to set up that appointment.

The pulmonologist does however want to do another sleep study for Bryce to check on the amount of apnea episodes he has during the night, how long they last, what type they are, etc.  Dr. N was glad to hear that we will be doing that because as part of the sleep study they attach electrodes to Bryce's head that will help us get another look at any seizure activity that might be going on.  So it will be good to check that out again as well. 

Outside of appointments, we have had some fun.  Yesterday was Bryce's Birthday.  I can't believe he is 7 years old.  It was a really low key birthday this year, but it did include singing the birthday song and lighting the candles many, many times since those are his very favorite part of a birthday celebration! 

Happy Birthday my big boy!

Crashing the System

Bryce and Annalise had their neurology appointment last Thursday.  I was hopeful, but not holding my breath for more information about the genetic sequencing being done by TGen.  Dr. Narayanan talked with Bryce and Annalise for a few minutes and caught up briefly with me on what has been going on with them lately.  Then he said, "Well, I want you to know we have not forgotten about your family.  The scientists at TGen are working really hard to get us some information."  As he sat down, he became a bit more serious and continued to tell me what has been going on over there.

Let me back up just a bit.  About a month and a half ago I had gotten a message from Dr. N  saying that there had been a glitch in getting our family's information all in one place.  A couple of weeks after that, I heard from one of the TGen scientists who said the same thing.  I didn't know what type of glitch they were talking about, but luckily at this appointment, Dr. N cleared things up a bit.  I'll do my best to explain!

He went into quite a bit of detail, even using the paper cover on the examining table to write things out as he explained them to me.  I will just give you the basics of what he said.   He said that TGen had first sequenced just Bryce and Annalise's exomes thinking that they would find something new along the AGS lines.  They only found what we already knew.  Next they sequenced John, since he is also a carrier of AGS, and put the information from the three of them together to look for anything new.  Nothing.  Next they tried sequencing me and one of our other children and adding us to the mix.  Still nothing.

While waiting for our appointment, Bryce entertained himself by pulling the cord out of this machine over and over again.  He would laugh every time he got it out.

At that point, Dr. N told them to basically stop beating around the bush (ha ha) and just to sequence the rest of our family's genomes so that  they could map it all out together.   So, that is what  they did...or at least tried to do.  The sequencing part of it went fine.  Then they tried to enter every one's information into the machine/computer (I'm not sure what it is) so that it could map everything together.  When they did that, the entire system crashed.  Yes, our family crashed TGen's million dollar machines.  Oops!  After multiple tries and multiple crashes, they decided that they may need to re-sequence everyone at the same time and then try again.  Basically, they would have to start completely over.  As they were getting ready to do this, one of the scientists came running out yelling that he had gotten it to go through!  Hallelujah!   I'm sure they were all very relieved!

That was about 2 weeks ago.  Since that time, they have gotten the results of the mapping back.  Dr. N went over how they narrow it all down, etc.  I won't go into that, but I will tell you what they know as of now.  They found about 10 gene pairs, or mutations (I think that is what they call them) that Bryce and Annalise have in common and that the rest of us do not have.

Once they get to that point, they look a those gene mutations and see what condition is connected in some way with these particular genes.  Then they are able to make a sure diagnoses.  Well, that is the way it is supposed to work.  However, in Bryce and Annalise's case, there is not one of those mutations that matches up to any known disorder that are in their database!  Yes, Bryce and Annalise very possibly have something that has not even been discovered yet.  I knew that was possible, but I didn't really believe that would be the case!

So, where do we go from here?  Well, TGen and Dr. N are now in the process of searching Data base's from all over the world to see if they can find any record of other people who have any of these gene mutations and symptoms similar to those of Bryce and Annalise.

 
We discussed the possibility of it being something caused by environmental factors, foods, or certain chemicals.  Because of the onset of their symptoms, it is very highly unlikely that this is caused strictly by an environmental factor.  (He told me of  a strange case he worked on where white matter depletion was caused by an environmental factor...weird stuff!)  He said that it could be that the combination of the mutated AGS gene and one of these other 10 mutations causes the symptoms that we are seeing.  It is possible that it may be an undiscovered form of AGS.  We just don't know at this point!

There are a few things that we do seem to know about "Bryce's syndrome"  as I've called it from the beginning.  We know that (at least in our 2 children) onset of the disease is at about 17 months of age with the child developing normally until that point.  We know that there is an initial period of rapid regression that begins with pain, irritability and possibly a mild illness.  We know that it affects the immune system.  We know that it causes trouble with inflammation and "lupus like" conditions.  We know that it causes "seizure like" activity.  We know that there are periods of rapid regression and periods of plateaus.  We know that it causes a child to have an extreme startle reflex and tonic neck reflex. We know that it causes central apnea as well as obstructive apnea.  Apnea episodes occur while the child is awake as well as while he is asleep.  We know that it causes spasticity  throughout the body.  Change in weather seems to increase the amount of pain caused by that spasticity.  We know that there is pain (in addition to the pain caused by the spasticity), although we are not sure exactly where that pain is coming from or what triggers the pain.  It is not constant pain, but random.  It appears that illness and fevers, even minor ones can cause severe fatigue and regression, some being temporary and some being permanent.  Good nutrition seems to be vital for maintaining, and possibly improving, their health, strength, and abilities.  Cognition does not seem to be affected.  Bryce and Annalise are very smart.  They are aware of everything that goes on around them.  Aside from their physical and neurological limitations, they are very much like other children their age.  

There are a few other things I have observed over the years with them, but I don't know if they really have anything to do with their condition or not.  Really, we just don't know a whole lot about what is going on with them and we have no idea what tomorrow or the next day, or any day into the future holds for them.  We have no idea how long they will be here with us.  It could be months or it could be many, many years.  Bryce and Annalise will continue to teach us as they continue to live their lives and take on their daily challenges like the warriors that they are. 

Dr. N assured me that he is not finished searching yet and that something may very possibly still turn up somewhere in someone's data base of information.  Only time will tell.  Until that day, we will continue to live life to the fullest and enjoy every moment of every day with each of our children. 

Latest Happenings

So much has been going on lately.  I'm going to see if I can sum things up in a nutshell for you all here.

Bryce continues to do amazingly well.  He continues to do things that we never thought we would see him do again.

 5 minutes with his head held high! 

 

Um, Yes...that is Bryce SITTING on his own.  Sitting was the first ability that he lost over 5 years ago!   I honestly never thought I would see this day!  Miracles do happen!

A little motivation goes a long way!

Just a couple of kids hanging out watching My Little Pony videos.

The only real issues we are having at this time are his vomiting episodes over the past few months, the increase of apnea episodes over the past few weeks, and seizure like activity that we are keeping an eye on.  We don't know what is causing either of these things to occur.

The vomiting issues began about 8 months ago.  Within this time he has had 7 vomiting episodes.  The episodes are strange because of the timing of things.  It goes kind of like this:  Around either 9:30am or 2:30pm, Bryce begins vomiting without warning.  This continues for about 4 hours with him vomiting about every 8-15 minutes.  The first 2-3 times are quite violent and bring up his most recent meal.  Then it turns to just mucus type stuff that he is vomiting and, during the last 5 episodes, he also vomited blood.  He becomes pale and lethargic very quickly and has to be suctioned each time he vomits since he is not strong enough to "get it all out" on his own and will begin choking easily.   Because it comes on so suddenly and he needs suctioning almost immediately, we now carry his suction machine around with him everywhere he goes.  During the night, Bryce moans and seems to be very uncomfortable.  About 1 in the morning, he begins running a low grade fever, around 101.  That continues until about 10:00 the following morning.  That entire day, Bryce is very lethargic and continues to appear to be in pain.  He sleeps most of the day and has no interest in what is going on around him.  That night, he sleeps fine and wakes the following morning good as new!  He is then fine until the next episode occurs.  No one else in the house gets sick, so we have ruled out a stomach flu.  Cyclic Vomiting Syndrome, among other things, is being considered.   For my own record, here are the dates of these episodes:

March 29
April 22
May 17
July 18
Sept 2
Sept 19
Sept 28

The apnea episodes are something he has dealt with for years.  He used to have them quite often, then he went for a period of time (almost a year) with only a few here and there.  Unfortunately, they have become quite frequent again.  These are times where he seems to stop breathing for a short period of time.  Scary stuff!

Well, this post seems long enough for tonight.  I will continue with Annalise's latest happenings and the latest in our genetic sequencing adventure soon.  Good night all!

Annalise Walks!

Today Annalise took her first steps for the second time in her life.  At the age of 17 months Annalise was walking very well.  In fact, she had just begun to run.  Then suddenly, she began to lose her balance and before long, she was no longer able to walk without support.  She began using doll strollers to help her balance and walk.  Soon that became too difficult as well and she began walking with a walker.

She has been working really hard for months on being able to stand without assistance.  In just the last couple of months, she has gone from only being able to stand for about 10 seconds to now being able to stand up to about 3 minutes at a time.  Today her PT Lauren was here working with her and so was Lauren's supervisor, Ray.  We were talking about the things she is now able to do and he suggested we see how she would do if we asked her to walk.  So he did and she tried to take off really fast.  She didn't get more than about a half a step before falling into Lauren.  Then Ray explained to her that she should try just taking one step and then find her balance and then take another step.  To go really slow, like a turtle.  So she did.  She ended up taking up to 7 consecutive steps while walking today.

By the end of the session, she was very tired, but she was very happy as well.  I was also very happy and I will admit, still in a little shock.

Now for those of you who know about Annalise's journey, you know that medically this is not supposed to happen.  We have believed for years that she and Bryce had Leukodystrophy and that once the skills were lost, they would never be regained!  Well, it appears that God and Annalise have other plans!  Today we truly witnessed a miracle.

To see some very cool videos of Annalise's first steps join us on Facebook

Visit From Dr. Narayanan

I just wanted to let you know that while we were staying at the Ryan House this past Thursday night, Dr. Narayanan stopped by to give us a quick update on where we are with the sequencing.  He said that he continually bugs the team to get the results to him ASAP.  I truly think that the TGen team will be very glad once our sequencing is finished.  :)  Anyway, Dr. N said that the current sequencing is complete and the team was working on getting all of the data compiled onto a one page spreadsheet.  Dr. N told them that he would like to have it done by Friday (yesterday) night so that he could take it home with him and begin analyzing it over the weekend.

That is all the news that I have so far, but I just thought I would let you know.  Hopefully soon we will have some more news/information.   We continue to pray for positive results!

Annalise's Results

Last Friday, Annalise had her MRI tests.  A couple of hours ago, I got an email from Dr. Narayanan.  Seriously, does that man ever sleep?  Anyway, here is the official report he got from the radiologist:

MRI is normal, MRA is normal, and MRS (spectroscopy) is normal.

Yes, you read that right.  Normal, Normal, and Normal!  Fantastic news, right?  Yes!  It is, don't get me wrong.  I am thrilled that, like Bryce, she too has shown progress in her myelination.  It gives me a new hope (again) that maybe our children don't have anything seriously wrong with them.  That maybe there is an easy answer and maybe even a cure!  I want to hold on to this hope, to not think any further.

But then I look around and the frustration sets in.  I want so badly to believe that everything is NORMAL with our children, but if this is the case, why is Bryce in a wheelchair, why can he no longer chew, suck, and swallow correctly, why does he stop breathing at times, why does he have to speak with me using his eyes instead of words,  why is he lying on the floor or sitting in a special supportive chair while watching his brothers run, ride their bikes, play ball, play video games and all the other things a NORMAL 6 year old boy would be doing?   Why do I still have two children in diapers?  Why is my daughter unable to run like she used to, why is it getting harder to understand her words instead of easier, why does she wake in the night because of pain and the inability to roll herself over or to get in and out of bed on her own like any NORMAL 4 year old can?

If everything is normal, why is it not?

Dr. N went on to share his thoughts:

"When I look at the MRI - I still have the feeling that there is some problem with the pace of myelin development.  There has definitely been some progress in myelination between 18 months and now; but just not at the normal rate I think.
This is also the same feeling I had when reviewing Bryce's latest MRI.  There is also the report compared to his prior MRI which suggested delay in myelination.  They say that the myelination patter is symmetric, and improved.  They also noted subtle prominence of the cerebellar folia (spaces between the ridges of the cerebellum).

I think this takes us out of the Aicardi-Goutieres syndrome group of disorders.  All the other classical leukodystrophies have been ruled out.  Still can't ignore the mild elevation in CSF neopterin in Annalise.Clinically, they both look like they have some white matter disorder."

He went on to tell me that he has one more hunch and will have to do some work to figure this out.  Didn't tell me what that hunch is, which of course makes me crazy curious and yet at the same time I don't want to know what he is thinking or I will research something else for hours and hours only to find out that it leads to another dead end.  He says that he thinks the best shot is to wait until the exomes on me and John are completed and then we will have a better idea.  I think he is right.  Hopefully this will be available in the next few weeks, he says.  I hope he is right.

I want to stay positive.  I'm trying, I really am.  I don't want to sound negative because the news that we have gotten about the myelin truly is wonderful news!  Definitely a blessing!  I am so thankful that this is what is happening in our children's brains.  

We truly have been blessed with a wonderful man as our children's neurologist.  He is working so hard and coming up short and never giving up.  Even though in so many ways, it feels like we are still so far away from knowing what is going on with our children, there is a part of me that believes the answers are right in front of us.  I can feel it!  If only we knew how to reach out and grab them.  

I know that when the time is right we will know.  I know that the Lord knows.  I know that we have family and friends on the other side helping us...both in finding the answers to our mystery and in helping us be patient until that time comes.  I definitely cannot see the whole picture.  I don't understand why our children have to go through all of this...especially if we do find out that it is something that can be solved, that with some small thing our children can be healed.  Wouldn't that be wonderful!  Oh how I hope and pray that this is the answer that we finally, someday soon will be given.  

We have been talking for a while now about looking into Make-a-Wish for Annalise.  Bryce had his wish granted back in 2010, one month before Annalise was "diagnosed".  It was wonderful and truly a blessing to Bryce as well as the rest of our family.  Something we will cherish forever!  Annalise loves Micky Mouse.  She loves water.  She talks about swimming with dolphins.  I think we will hold off just a bit longer.  Who knows, maybe she won't even qualify for a wish!  Wouldn't that be crazy...and wonderful!

All I know is that through this journey I have met some incredible people.  People who, very likely, I never would have met otherwise.  I have learned things that I never would have learned.  I have become a person who I never would have become without this part of my life.  My husband and all of our children have done the same.  I feel like everyday, even as I continue to learn, the less I know.  One thing I do know for certain though is that there is something so much bigger than us out there.  I know that we have a loving Heavenly Father who is fully aware of who we are and what we need.  There is a plan and every single one of us has a very important role in that plan.   

Not Leukodystrophy

Okay, I know I said in my very last post that I was not going to be continuing with this blog.  Guess what?  I have changed my mind.  I need to continue with the updates on our quest here on this blog...at least until we have some answers.  I will keep the facebook page going because it is a great place for quick day to day updates, pictures, and videos.  This blog will be used more specifically for updates and news on the actual journey to find answers to this mystery.  Then our family blog will be used for, well, everything, including more of my thoughts and feeling on the information I post here!  

So, on to the latest updates.  Bryce had an MRI/MRA last Wednesday.  Thursday morning when I woke up, I found that I had an email from Dr. Narayanan.  He had compared this MRI/MRA to the MRI's done in 2008 and 2010.  He had also read the official report.  He let me know that the MRA was totally normal.  Great news!  This was the first MRA Bryce has had done, so it was good to know that everything looked good on that.

Then things got interesting.  He said that the report stated that the MRI did not show significant abnormalities in myelin, and showed signs of continued myelination!  That is huge.  Do you know what that means?  Somehow, Bryce's brain is actually growing myelin again!   Awesome!   Totally unexpected, but awesome!

Another comment was that the folia in the cerebellar hemispheres were slightly more prominent than before-these are like the sulci in the brain.  I had to google that one and ask some additional questions of Dr. N, but yeah, it appears that this is good news too.

Then Dr. N shared his feeling on the results:

1)  Even though the myelination is improving, it doesn't quite look like it should for a 6 year old.
2)  Not a Leukodystrophy
3)  Still waiting on exomes from the rest of the family.

He then kind of thought out loud for a bit and said, "back to the drawing board".  He asked me to contact our pediatrician and get all of the neurology consultation notes from before Nov. 2010.  He is going to start again from the beginning, rethink through everything, and look at all the data again.

Since this email left me with a few new questions, I emailed Dr. N and got another email back.  I'm posting it here, because it is full of information and helped to explain a bit more of what is happening with Dr. N and the sequencing at TGen.

Dear Tammy:
The latest from TGen.
1.  In the first sequencing runs (whole exome sequencing) they did Bryce and Annalise.  They identified the same SAMHD1 variant that we knew about already.
2.  Based on our feeling that this was too much of a coincidence (clinical suspicion of AGS, elevated neopterin in Annalise; absence of calcifications), we decided that the next step was to see if there was a difference in the expression of the SAMHD1 genes (levels) between dad and the two affected children. We chose dad, because he also has the one SAMHD1 variant.  The idea was that if in the children, the levels of normal SAMHD1 was way low, then this could be why they had symptoms of white matter disorder, without us finding a second mutation.  The RNA sequencing on dad, and two affected children is done; still being analyzed, but a quick look at SAMHD1 levels shows that they have normal levels of the copy that they inherited from you (mom).  so this is not the answer.
3.  We had planned on sequencing (whole exome) mom, dad, and one unaffected sibling.  The preparation has been done, and they will go onto the machine next week, and we should have results in 3-4 weeks.  When we get this, we will analyze the entire family from scratch - without a preconceived notion that this might be AGS or might be linked to the SAMHD1 variant.  Just that it is autosomal recessive, and causes spasticity.
4.  The MRI result on Bryce just makes me question everything - including the idea that this is AGS; it doesn't look like a classical leukodystrophy. But his symptoms with loss of skills, spasticity, fits the AGS model.  Maybe something new.

I have to study this all over again, and having my early notes will help me.
I hope I am explaining things clearly to you.
Hopefully, we'll have more data in 3-4 weeks, and we'll get another attack at solving this puzzle
Vinodh

So there you have it.  You know as much as I know.

Exactly 5 years from the day Bryce began showing symptoms of regression (July 2008), we are back at square one.  The journey is long.  The mystery continues...