Sunday, July 21, 2013

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...

3 comments:

Shalyse said...

You seem to have a great set of doctors working hard for you. What a blessing! We continue to pray for you!

Ryder Hauer said...

As frustrating as it all is, I am so thankful that we were both on the leukodystrophy track and found each other!!!! Praying for peace of mind and answers Tam!!!Love you so much!!

Lex-a-roo said...

I'm glad I found your blog. I have a daughter that has been diagnosed with AGS so I've been looking for families to connect with. But it looks like you might not be looking at AGS now? Anyway I get the impression that you are LDS. I'm LDS too and if you're up to chatting via email that would be so nice. lextoland- g-mail