Oliver's last scheduled appointment with the metabolics doctor during his clinic time in Medford was two weeks ago. We arranged for Joel and I to go instead since we are still wanting to understand the root cause of Oliver's medical conditions for several reasons. This particular doctor had full access to the medical charts but never met Oliver, so we took photos and my home medical binder with us.
It was very strange being there without Oliver. I could feel myself shifting into "medical/doctor discussion mode." Previously this was accompanied but a sober but driving motivation to solve the mystery to fix my son and the thrill in stretching my brain to understand the conversation. This time it kept feeling empty, silly, and foolish, even though we were still there with a purpose (to understand the risk to future biological children).
This was the first follow-up visit since the big metabolics/mitochondrial genetic panel came back without showing any abnormalities. Taking this result into consideration, along with his particular (extensive) experience with pediatric mitochondrial diesases, the doctor was inclined to think that Oliver did NOT suffer from a mitochondrial disease. A mito disease would explain all the particular problems he had at the end, but it would not be the best explanation for the progression of Oliver's condition. (You can skip the details if you like and jump to the conclusion of the visit - the paragraph beginning with "SO".)
In this doctor's experience, pediatric mitochondrial diseases do not first present as structural deformations, but rather are identified after some neurological problem, like seizures, is observed, usually after the child is several months old at least. The root problem is a chemical processing disorder that eventually makes itself known as it affects multiple organs. The chemical imbalances in the body lead to the neurological problems and eventually can cause trouble for the kidneys (which try to fix the chemical imbalances), heart, eyes, and other high energy demanding organs.
For Oliver, the difference is that the structural problems were seen first - his deformed kidney and various heart defects specifically. These organs develop very early in pregnancy, and their function, or lack thereof, affect the baby very early on. Poorly functioning kidneys cause chemical imbalances as well, and if not fixed they lead to neurological problems, breathing issues, stamina and strength issues, and all the other problems Oliver dealt with. So, while Oliver's condition towards the end of his life looked very similar to a mito disease, considering his overall progression and his normal metabolics genetics panel, it may be that his primary problem was actually a genetic mutation that affected the development of his kidneys and heart, and the poor function of these organs lead to the chemical imbalances that caused all of his other problems.
There are family of known genetic disorders that are linked to concurrent kidney and heart deformations, but we had already tested for these back in August and none of them came back positive. Also, these type of kidney/heart genetic mutations are genetically dominant (each offspring has a 75% chance of inheriting the disorder), so they are easily identified in family lines and among siblings. There is no family history of anything like this in either Joel's or my family.
SO, all that to say that the doctor is inclined to think that this is a rare case of an unknown, spontaneous mutation that occurred just in Oliver, either when the components of his genetic code were written or when they were being copied at his very beginning.
We are considering the option of doing an exome sequencing of Oliver's DNA. This process will sequence the part of the DNA that codes for proteins. It covers approximately 200,000 genes (in total we've looked at maybe about 300 of Oliver's genes so far), which is only between 1 and 2% of the total DNA code but has been seen to include the vast majority of known mutations that cause harmful disorders. We are still waiting to hear about the final price tag on this sequencing, and are undecided about if we will pursue it.
It was very strange being there without Oliver. I could feel myself shifting into "medical/doctor discussion mode." Previously this was accompanied but a sober but driving motivation to solve the mystery to fix my son and the thrill in stretching my brain to understand the conversation. This time it kept feeling empty, silly, and foolish, even though we were still there with a purpose (to understand the risk to future biological children).
This was the first follow-up visit since the big metabolics/mitochondrial genetic panel came back without showing any abnormalities. Taking this result into consideration, along with his particular (extensive) experience with pediatric mitochondrial diesases, the doctor was inclined to think that Oliver did NOT suffer from a mitochondrial disease. A mito disease would explain all the particular problems he had at the end, but it would not be the best explanation for the progression of Oliver's condition. (You can skip the details if you like and jump to the conclusion of the visit - the paragraph beginning with "SO".)
In this doctor's experience, pediatric mitochondrial diseases do not first present as structural deformations, but rather are identified after some neurological problem, like seizures, is observed, usually after the child is several months old at least. The root problem is a chemical processing disorder that eventually makes itself known as it affects multiple organs. The chemical imbalances in the body lead to the neurological problems and eventually can cause trouble for the kidneys (which try to fix the chemical imbalances), heart, eyes, and other high energy demanding organs.
For Oliver, the difference is that the structural problems were seen first - his deformed kidney and various heart defects specifically. These organs develop very early in pregnancy, and their function, or lack thereof, affect the baby very early on. Poorly functioning kidneys cause chemical imbalances as well, and if not fixed they lead to neurological problems, breathing issues, stamina and strength issues, and all the other problems Oliver dealt with. So, while Oliver's condition towards the end of his life looked very similar to a mito disease, considering his overall progression and his normal metabolics genetics panel, it may be that his primary problem was actually a genetic mutation that affected the development of his kidneys and heart, and the poor function of these organs lead to the chemical imbalances that caused all of his other problems.
There are family of known genetic disorders that are linked to concurrent kidney and heart deformations, but we had already tested for these back in August and none of them came back positive. Also, these type of kidney/heart genetic mutations are genetically dominant (each offspring has a 75% chance of inheriting the disorder), so they are easily identified in family lines and among siblings. There is no family history of anything like this in either Joel's or my family.
SO, all that to say that the doctor is inclined to think that this is a rare case of an unknown, spontaneous mutation that occurred just in Oliver, either when the components of his genetic code were written or when they were being copied at his very beginning.
We are considering the option of doing an exome sequencing of Oliver's DNA. This process will sequence the part of the DNA that codes for proteins. It covers approximately 200,000 genes (in total we've looked at maybe about 300 of Oliver's genes so far), which is only between 1 and 2% of the total DNA code but has been seen to include the vast majority of known mutations that cause harmful disorders. We are still waiting to hear about the final price tag on this sequencing, and are undecided about if we will pursue it.
I am Abigail O.'s sister, Becky. I had heard of dear little Oliver from her, but this is my first visit here to read more about him and your family. I too have gone through periods of research looking for answers about our one daughter in the last three years, so I can relate to that aspect to some degree. I can only imagine your mother's heart and the deep well of feelings it contains. I am touched by all the time it took to care for your little boy in so many ways as only a mother can. I have prayed for you in this time, and just wanted you to know that.
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