Rather than me re-writing everything, let me share a summary (minus a few tests from the first couple of days) that Greta, my wife, put together from our visit to the Undiagnosed Disease Program at the National Institute of Health. Stay tuned through the end, I’ll add in some more information giving an update of where we are at now, 1.5 years after the visit.
“Well, so much for keeping you all updated throughout the week! I ended up with strep throat, and that combined with all Kipp’s tests was exhausting. I will try to resume where I left off.
On Tuesday after his clinical photo shoot, Kipp had a forearm skin punch taken for research purposes. Then, he had a visit with a neuro-opthalmologist. The results of all the ophthalmology tests were normal. Then, Kipp had a brain MRI which showed a completely normal brain with normal brain stem and normal cerebellum, which confirms that Kipp’s ataxia is not the result of a problem with his cerebellum. We again went out on pass Tuesday night to stay at our hotel in Bethesda.
On Wednesday, Kipp had a spinal MRI and a lumbar puncture. The spinal MRI showed a normal spinal cord with no lesions of any kind. The lumbar puncture was the procedure that Kipp was most anxious about because it can result in a pretty bad headache for some people. After the Radiologist got the needle in with x-ray guidance called fluoroscopy, I was able to join Kipp in the room to help him relax as his cerebrospinal fluid dripped out. For some reason, Kipp’s dripped at a particularly slow rate and they had to tilt the table up to try to get as much out as possible. They wanted about 18 cc’s, but they ended up with only 13. Kipp handled it very well, although he got very hot during the procedure. We got some wet towels on his head and face, and that helped. After the lumbar puncture, we went back to his hospital room where he had to lay flat for 2 hours to prevent headache. Fortunately, he did not get the headache he was so worried about! Later in the afternoon, a pediatric neurologist came to evaluate Kipp. They wanted her to take a look at him because his symptoms began when he was young. She was stumped by his presentation, just like everyone else.
Wednesday evening, we had an opportunity to meet Dr. Gahl, the head of the Undiagnosed Disease Program. We had a nice visit with him, and he interviewed us briefly about Kipp’s case.
Wednesday night, Kipp decided to stay at the hospital because he had another 24 hour urine screen being collected, and he was on call for a spinal MRI with contrast. There was a possibility that they could call him as late as 11 pm for the MRI. I went back to our hotel and crashed so I could be there early the next morning.
Thursday was a very busy day. First thing in the morning, Kipp had more blood work done to rule out mitochondrial problems and to measure cellular inflammation. Then, he had a barium swallow study with a speech pathologist and a speech evaluation. The swallow study was normal. And she found that he does not have a tremor in his voice, but an intermittent vocal spasm. It was interesting to learn the correct name for his vocal symptoms!
After the swallow study, Kipp quickly ate breakfast before Rounds when about 30 people (students, doctors, and researchers) crowded into his hospital room so that Dr. Landis (his neurologist) and Dr. Gahl (head of UDP) could discuss his case. Then they demonstrated some quick neurological tests such as finger to nose testing (Kipp has difficulty with his with his eyes closed only) and deep tendon reflexes (Kipp’s are absent). Then, they had Kipp walk for everyone.
Following Rounds, Kipp met with an OT and PT. The OT made some specific recommendations for improving safety in our bathroom at home, and the PT made recommendations for Kipp to try Swedish AFO’s and for what type of exercise to work on.
Then, Kipp had an EKG and an echocardiogram; both showed normal heart function. They want to carefully look at his heart because of the association of cardiac myopathy with Friedreich’s Ataxia. Then, he had an abdominal ultrasound which showed that his organs are all normal, which helps to rule out mitochondrial problems. His last test of the day on Thursday was a spinal MRI with contrast, which was normal. Thursday night, we went out on pass to our hotel.
Friday morning, we came back to the hospital for his wrap-up with Michelle (N.P.) and Dr. Landis. They reviewed all the test results from the entire week. Basically, all the tests were normal, normal, normal! All the lab work showed that Kipp is healthy and normal. He does not have problems with his mitochondria. He does not have cellular inflammation of any kind. The MRI’s and other nervous system tests show that Kipp’s nervous tissue including his brain and spinal cord and peripheral nerves are all intact. There is no tissue damage to those structures. However, Kipp’s symptoms are consistent with central nervous problems of some kind, more specifically problems with dorsal columns and pyrimadal tract of his spinal cord.
After reviewing all the tests with us, then Dr. Landis reviewed his hypothesis for Kipp’s diagnosis. They think Kipp has a variant of Friedreich’s Ataxia that is different from any other known type of Friedreich’s. So, in order to better explain this, I will first give you some background on Friedreich’s Ataxia. FA is the most common type of inheritable ataxia because many individuals (especially those with European descent) are carriers. It is a genetic disorder that is an error in the gene/DNA for the frataxin protein. Frataxin is a protein that is localized to the mitochondria. The function of frataxin is not entirely clear, but it seems to be involved in assembly of iron-sulfur clusters. It has been proposed to act as either an iron chaperone or as an iron storage protein. FA is a homozygous recessive disorder, meaning that in order for the disease to be present, both parents must contribute their recessive gene to their child. Up to this point in time, there are two known types of Friedreich’s Ataxia. To explain these types, I have to give some information on the structure of DNA. DNA is made up of coding sections called exons and non-coding sections called introns. Exons contain the information to make proteins correctly, and introns are spacers that control the rate at which proteins are produced. In 96% of FA cases, the frataxin genes inherited from both parents have normal exons and extra long introns called GAA expansions. Because the exons are normal, the frataxin protein is made correctly, but because introns are extra-long, it takes longer than normal for the frataxin to be manufactured by the cell. Eventually, the body runs short on frataxin, and severe neurological symptoms develop that are progressive over time and usually lead to a shortened life span. In 4% of FA cases, the frataxin gene inherited from one parent have normal exons and extra long introns and the frataxin gene from the other parent has abnormal exons and normal introns. This means that some of the protein made is normal, but at a slower rate. And some of the protein is made at a normal rate, but it is an abnormal protein. Symptoms can be more variable in this type of FA.
Dr. Landis believes that Kipp inherited frataxin genes from both his parents that have normal introns and abnormal exons, meaning that he produces the frataxin protein at the normal rate, but the protein being made is abnormal. This would explain why his frataxin levels in his body are normal, but he still has symptoms. Dr. Landis believes that if this is true, then Kipp has a new and unique type of FA, and so far what we can see in Kipp’s physical presentation is a more benign course of symptoms and progression. Currently, there is no known cure or treatment for FA. There have been studies with some drugs and supplements, but so far nothing has worked.
In order to confirm or disprove this hypothesis, Kipp’s DNA has been sent to a commercial lab for quick evaluation of the entire frataxin gene (previously he had genetic testing for this but it looked specifically for problems with introns). We should have results from this DNA testing within 4-6 weeks.
If this is correct, then we have a diagnosis. If not, they will proceed with sequencing DNA for Kipp’s whole family in order to find another cause. This process would take 4-7 months.
So, Kipp and I wrapped up our Friday by checking out of our hotel in Bethesda. We took the metro to downtown DC where we stayed in a really nice hotel right across from the White House. Then, we relaxed and did some sightseeing before flying home Saturday evening.
Again, thanks for all your love, support, and prayers throughout the last week! I hope I didn’t bore too many of you with all the details I shared. I will let you all know when we hear something more about the DNA testing.”
This visit to the NIH was a breath of fresh air, of sorts, for me. I’ve been to specialists of all sorts through the years, at least all the top ones that have been more directly available to me. Each one begins hopeful, then, after I repeat all the familiar tests, they run into a wall. I don’t fit nicely into a box, the standard and even extraordinary templates, I defy. I am a non-conformist! The team with the Undiagnosed Disease Program at the NIH picks up where these more standard tests and ideas leave off, they try to dig further, and for many people, myself included, that gives hope after having others give up on the puzzle.
Results from the frataxin gene tests came back, negative, again. This has seemingly ruled out the hypothesis we left the NIH with, that I may have a 3rd, undiscovered type of Friedreich’s Ataxia (FA). After this conclusion, DNA samples were sent in from each of my family, brother, father, mother, and myself, to have our entire exome sequenced. And we wait. The DNA sequencing has finished, the results have been entered into the Human Genome Project, and we wait for the team at the Undiagnosed Disease Program to get a chance to dig through the sequencing, looking for any possible variation between myself, and the rest of my family, as a clue for the next thread to pull on.
Starting out this blog last week, I had some pretty good ideas of the direction I wanted to go. Your response has exceeded anything I could have expected, and I am amazed at how quickly I have been able to begin networking with others. It seems, at this time, that I don’t have Friedreich’s Ataxia, despite that being the first thing any specialist thinks of when seeing me. But, I do have an ataxia, yet to be pictured. The FA community has done a tremendous job of bolstering support, and I already feel at home with this group. In the coming days, weeks, months, and years, I will be doing what I can to be a part of and help the mission of this community, starting with thoughts of being a part of Ride Ataxia NorCal, May 30, 2015, and continuing to build a connection with The Friedreich’s Ataxia Resarch Alliance (FARA).
If you or anybody you know, might be interested in helping get Greta and I get to rideAtaxia Norcal this year, or want to help with sponsoring my ride, or any other rider, please get in touch with me, either through this blog, or one of my other connected social website contacts. If there is enough interest, I’ll get a support page setup with more information on how you can help this great cause.
Thank you for sticking with this lengthy post and thank you for your support.