What a whirlwind of a trip. We departed Atlanta this morning and for the first time of our many departures from this city, I have some hope and optimism. I have a renewed desire to continue the fight, and a renewed desire to continue the voyage wherever it may take us.
We met with Maureen Starnes, Dr. Shoffner's Nurse Practitioner, yesterday for Spencer's appointment. She's an excellent clinician. She's compassionate and intelligent. She reviewed the data with us that confirmed his mitochondrial dysfunction/disease. I questioned the reliability of the data, any false positives, sensitivity and specificity of the enzymology testing that was done looking for any possibility that the data could be flawed. The instability of the various and multiple enzyme supercomplexes, family history, and extremely high lactic acid level all support the diagnosis. She reported that Spencer's mitochondrial disease was caught extremely early before any major events or significant damage had occurred. No one would have even checked him for this disease if two of his siblings didn't have mitochondrial disease. This really is a blessing! I am cautiously optimistic about Spencer.
Spencer still can not participate in sports at the level he is used to. It is extremely important for him to stay active and to exercise. We are going to do some experiments with him to see how much exercise he can tolerate. We are going to have him exercise at moderate to intense levels and repeatedly check his plasma lactic acid levels and CPK levels (creatinine phosphokinase an enzyme that is found in the blood when muscles break down). Spencer is doing ok with everything. He is an amazing young man!
We were full of questions about his prognosis, nature of his particular disease, and how to best proceed. She believes his diseases is completely different than Seth's and Sydney's Leigh's Disease. We compared data between them. She also stated she did not believe Spencer's disease would be progressive or degenerative with some qualifiers--that he takes care of himself and takes the supplements. Another qualifier is that mitochondrial disease is unpredictable but all the evidence to date did not point to his disease being progressive. This was a relief! She stated we will watch him very closely.
She reported there has been an explosion of new data, new methods for searching for genes, and potential treatment options. She again mentioned the clinical trial that our family will most likely participate in. She stated that within the next couple of months, they will be able to analyze and sequence up to 800 of the mitochondrial genes. This is amazing and exciting progress! I am hopeful we will find the genes responsible within the next several months.
I remember the first time I learned about the cell back in 1995. The human genome had not been sequenced at that time. I was in biology 130 at BYU with Professor Gary Booth. I was completely fascinated with the cell. I was amazed how everything was so organized. I remember learning about genetics. How the genes were highly organized in the nucleus of the cell on large beautiful molecules called DNA (deoxyribonucleic acid). When something needed to be replaced, fixed, or created again, it would all start with the genes in the nucleus of the cell.
The gene would be transcribed then translated then the protein would be made. The protein would then be modified, packaged, and delivered to its appropriate place so it could help the cell function and survive. I was so fascinated and almost obsessed with this beautiful process. I felt like I was transforming into a true nerd.
I distinctly remember Professor Booth speaking about the mitochondria calling it "the powerhouse of the cell". Learning how important this organelle was. Learning that one of its main functions was to convert the food we eat to a usable energy source called ATP through a multistep process that started with Glycolysis then to the Kreb's Cycle, then to oxidative phosphorylation. (I remember thinking that if I ever owned a bike shop, I'd call it "Kreb's Cycle Shop").
Little did I know, that my daughter Sydney who was around 1 year old at the time had major defects in her mitochondria. Little did I know, my future children would all suffer with multiple mitochondrial problems all in the oxidative phosphorylation portion. Little did I know that there were multiple genes that were defective and this would cause problems with the proteins that would be needed to convert the food they eat into the usable energy source called ATP. As excited and fascinated as I was to learn about the cell, genetics, and cellular energetics, little did I know how much heartache and sorrow these would cause in the future. Little did I know that this little organelle would change my life!
Now time for a little Cell Biology lesson. There are approximately 20,000 genes in the entire human genome (called nuclear genes). These genes are located on chromosomes in the nucleus of the cell. Chromosomes are made up of DNA. You have 23 chromosomes from your mother and 23 from your father. You also have DNA in your mitochondria. This mitochondrial DNA is only from your mother and its function is to help build only a small portion of the mitochondria. The majority of the genes to make the mitochondria come from the nuclear DNA not the mitochondrial DNA.
Over 1,000 of the 20,000 total nuclear genes are used to make mitochondria. That is 5% of all our genes code for some protein used ONLY in the mitochondria. This alone tells us how important mitochondria are, yet relatively, very little is known about it.
As I have mentioned in the past, I love Moby Dick. I read this book during a time when I was dealing with a lot of shame and other problems in my life. I'll use another Moby Dick analogy. Searching for these genes has seemed analogous to Captain Ahab and his whaling boat the Pequod searching for Moby Dick in the vast thousands of miles of open oceans.
We have two whaling boats (labs) looking for these genes. None of the captains (our doctors) are like captain Ahab (although a lot of doctors are similar to him). One is a private company called T Gen located in Phoenix which has already looked at our whole family's genome and haven't found any mutations, deletions, etc. Dr. Narayanan, who is overseeing the gene search at T Gen, told us they are looking again with newer technology. Dr. Narayanan also said to us that Dr. Shoffner is one of the world's foremost experts in Mitochondrial Disease and to trust him and to listen to what he says.
I feel fortunate to have Dr. Shoffner as the other captain of the whaling boat. I pray daily that these two captains of these whaling boats will be guided and directed and God willing help find a cure for our three children and thousands of others who suffer from this disease with NO cure and NO effective treatments.
With the news that Maureen told us on this trip, it's as if Captain Ahab and his whaling ship the Pequod have now gone from multiple shipmates all keeping watch for Moby Dick to using Sonar and GPS technology for the search and navigation. It's as if we have gone from the use of whale fat for fuel to burn in the lighthouses to a cleaner, safer, alternative fuel source. It's as if we may be beginning to abandon the whaling ships altogether. ( Maybe not quite yet. I still like using this analogy).
My closing thoughts. While Maureen stated there was an "explosion" of new developments within the last few months, I want a Big Bang type explosion for this disease. Dysfunction of mitochondria has been linked not only to Primary Mitochondrial Disease (like my children have), but also to Alzheimer's Disease, diabetes, Autism, Parkinson's disease, fibromyalgia, chronic fatigue, just to name a few. I want to do whatever I can to help. What my role is, I don't fully know at this point other than being the best dad and husband I can be, raising awareness of this disease and finding ways to increase funding for research.