Friday, June 16, 2017

The Ghost Has A Name...RANBP2

I wrote a blog post not that long ago about fighting a ghost...well, I think we found the ghost...and it has a name...RANBPD2. This came out of left field for us last week at our long awaited genetics appointment. This post is long and detailed and as much for my own processing as anything else.

Tuesday 6-13-17, was our appointment with Dr. Muge Calikoglu, a brilliant geneticist who has been able to diagnosis incredibly complex medical cases. She recited to us a brief medical history of Oliver, perhaps more thorough than anyone else ever has and then she launched into what she found in an analysis of 146 of Oliver's genes. Before she started, she asked if she could clear off the exam table so she could draw on the tissue type paper on top of it. Andrew and I leaned in as she explained Oliver's very complex genetic situation and honestly, much of it went over our heads. When everything was finished over an hour later I delicately folded up that tissue paper and put it in my purse. Sometimes it felt like she was speaking a foreign language as she plowed through research studies she had printed out for us and her theory of what all this meant for Oliver. To say we didn't see this coming would be an understatement.

She said Oliver does not have MNGIE and only has secondary Mitochondrial Disease, caused by other issues we’ll elaborate on. She emphatically said Oliver is not “dying right now from Mito”, but he is also more medically fragile than we previously knew...what bittersweet news.

The most significant revelation on Oliver's genetic test was found on three genes. People typically have 8-10 disease gene variants among their 22,000 or so genes. Oliver has three of “unknown significance” (which means his variation has never been seen before, so they can only theorize how they affect his health) on RANBP2. There are a few reasons this is important:

1- RANBP2 happens to be on the mTOR Pathway, very close to Tuberous Sclerosis (very interesting)
2- RANBP2 is a gene that helps control the pores in your cells (Here is a link to an article you can understand about how important your pores are). It also is involved in your energy maintenance and protein import and export.
3-  Oliver has one copy of RANBP2, if he had two, he’d be in much worse shape. The question is, how does having one variation interact with his TS diagnosis?
4- Dr. Muge has recommended that we keep Oliver out of school for flu season and/or when illness is more likely. She is concerned what happened this fall could happen again. She said something rather innocuous could “tip him over.”

The RANBP2 gene (when there are 2 copies) causes the brain to attack itself called Acute Necrotizing Encephalopathy. Her working theory is that some kind of infection triggered this one gene in Oliver, and that is why his body basically began shutting down this winter. This is a theory, but it does make some sense. It also would explain why his lactic acid was higher than expected, pointing towards some kind of infection. She told us that they don’t know everything yet about this gene, or how it interacts with the body. They do know that when triggered, it can cause cell and nerve destruction.

She reminded us that the million dollar question is, “If you carry this gene, plus have TS, does that combo explain everything?” It might. She doesn’t have enough evidence to be certain. When she looks at this gene in relation to known pathways, it sits right there as a susceptibility agent. But proving all this is next to impossible.

What does this mean moving forward? Practically speaking, we want to keep Oliver away from illness, especially the flu. Dr. Muge said the flu could be fatal if that faulty gene gets activated again. We will likely continue to keep him out of school in the fall, which is different than what we had thought before the appointment. The kids in Ollie’s class are adorable and great, but keeping germs to themselves is a bit unrealistic.
She also told us that the damage done by his near death experience this winter could have had some irreversible effects. She said we shouldn’t write off his “breath holding” (which is happening again) as just behavioral...she mentioned that the pons part of his brain could have sustained damage, and an EEG can’t pick up on all seizures (especially sub clinical ones). We are considering this and trying to keep more careful notes about the breath holding.

Since she thinks we are probably dealing with secondary mitochondrial impact we are going to try to minimize stress. She suggested we not try ABA therapy with him at this time, due to the stress and rigor involved with its implementation. She reminded us that years of seizures and the prolonged hospitalizations, time in the ICU, etc., has caused his little body to be very stressed. So we will keep trying to eliminate stressors and conserve his energy.

We are still having issues with pain management and his food regulation. On certain days he eats well by mouth, almost as if he is starving. On other days he wants to eat, but can’t swallow. These ongoing changes in his brain are possibly a combo of hormones, changes from TS and perhaps med interactions.

We talked at length about the changes we might expect during puberty, and had some hard conversations related to the level of caregiving he may require. She said puberty is downright brutal for most medically fragile kids. The flood of hormones to an already damaged brain can be another tipping point like the one we hit this winter. The average age of puberty for a white boy in the US is 9 years old. Oliver is 8.5 years old now. There is no way to predict when the hormone flood will start as every kid is different, but it isn’t as far away as we had hoped it would be.

Whew....if you read this far, I wish I could give you a big hug. It took me forever to write this post so I can only imagine how you felt trying to read through it. The struggle is real for those of us that find ourselves as mommy scholars.

“Our Father refreshes us on the journey with some pleasant inns, 
but will not encourage us to mistake them for home.” 

For any genetics folks out there who want the details:

RANBP2, Autosomal dominant, c.560 A>G, p.His187Arg (H187R), Variant of Unknown Significance

ETHE1, Autosomal recessive, c.184 G>A (NM_014297.3), p.Ala62Thr
GTPB3, Autosomal recessive, c.169 G>C (NM_133644.3) p.Ala57Pro


amanda bowden said...

Your strength inspires me so much <3 <3 me and Christopher pray for you guys every night!

Cathy Poulos said...

Stephanie - I find your writing incredibly good - detailed but filled with your heart emotions so that reading between the lines gives a small bit of insight of what you are dealing with. I appreciate the medical details in helping me understand what Ollie is dealing with, but you go far beyond in your ability to help me understand what you and Andrew are dealing with, well as close as I can for I know that it is only through walking in your shoes that I would ever be able to comprehend the physical energy, turbulent emotions of fear, love and faith that you pour out each day! You are all incredible and a witness to Christ in HIs suffering and love for us. Prayers continue for you and Andrew's energy and health as well as Ollie's. We love you so much! Cathy

Anonymous said...

All three of you together are a beautiful picture of a beautiful family.

I read it. You did a great job explaining, re-capping. I feel that I understand where you all are at. Sending prayers to all three of you for the strength it takes to hang in there, and for comfort, and for some joy.