Wednesday, August 29, 2012

Spencer Update--Hope

Spencer Yosemite National Park July 2012 Half Dome in background

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.

Electron Microscopy of mitochondria (top) and drawing of mitochondria (bottom)

Monday, August 27, 2012

"Dad, I'm confused"

So we are off to Atlanta again.  I've lost track how many times we have made this trip.   It's a 3 hour drive to the airport and a 4 hour flight.  This trip is for Spencer.  The 3 other kids are home with Grandma and Grandpa Warnick.  Last night we had a pharmacology session with my in-laws as we explained the medications and supplements that are other children need to take.

I asked Spencer the other day how he was doing with the news of his confirmed diagnosis of Mitochondrial Disease.  He said:  "dad, I'm confused".  What do you say to that answer?

I wonder if these are his thoughts:   I'm headed back to Atlanta to hear what my future holds.  I'm going back to hear I have a disease that has no cure and no effective treatments.  I'm going back to Atlanta to learn more about this incurable disease--is it going to be progressive and degenerative?  How long will I live?   Do I have a form of mitochondrial disease that is mild and only cause bad headaches?   Essentially, I am headed for years of uncertainty, a lifetime of taking medications, and a lifetime of continuous doctor's appointments.

As a parent, I feel so powerless!  I wish I could take this from him and my other kids.  The emotional pain he is experiencing must be terrible.  It was so different with Sydney and Seth when they were diagnosed.  Sydney has poor insight and Seth's was congenital.  Spencer is so intelligent and athletic. 

As he transitions to his new life, Is there any place, anything that can provide solace during such a time of turmoil and uncertainty?  The only thing I know of is to look Heavenward.  As I've mentioned in prior postings, I have tried other sources of peace which are not true peace.  The issue I'm having at this time is I've NEVER dealt with anything like this ever before.  I have never been challenged so deeply and to the heart and soul of my existence.

Grove of Sequoia trees Yosemite National Park

Last Friday, I woke up around 11 and noticed the light was on in Spencer's room.  I went in to see what was going on, and found him sitting in bed reading his scriptures.  I gave him a goodnight hug, walked back to my room with tears in my eyes.  "...and a child shall lead them...".  I'm no scriptorian, but I know there is a scripture that says something like that.  He is an example to me and anyone reading this blog on how to handle adversity.  I feel so blessed to have a  son like him.

As 3 out of 4 of my children have been diagnosed with Mitochondrial Disease, my focus in life has changed dramatically over the past several months from passions in cycling and other forms of fitness to raising awareness and helping find a cure for Mitochondrial Disease.

Sunday, August 19, 2012

Life on the Pequod...The Tempest is Raging on

"Call me Ishmael. Some years ago- never mind how long precisely- having little or no money in my purse, and nothing particular to interest me on shore, I thought I would sail about a little and see the watery part of the world. It is a way I have of driving off the spleen and regulating the circulation. Whenever I find myself growing grim about the mouth; whenever it is a damp, drizzly November in my soul; whenever I find myself involuntarily pausing before coffin warehouses, and bringing up the rear of every funeral I meet; and especially whenever my hypos get such an upper hand of me, that it requires a strong moral principle to prevent me from deliberately stepping into the street, and methodically knocking people's hats off- then, I account it high time to get to sea as soon as I can. This is my substitute for pistol and ball.   With a philosophical flourish Cato throws himself upon his sword; I quietly take to the ship. There is nothing surprising in this. If they but knew it, almost all men in their degree, some time or other, cherish very nearly the same feelings towards the ocean with me"

Those who have read Moby Dick will recall these words.  I love this book!  The reasons Ishmael decides to stop what he is doing in his life and go on his journey aboard the Pequod are similar to the way I have been feeling.  Unfortunately, I can't just get on a boat and sail away.

There have been many days during this journey over the last few years that are memorable in good and bad ways.  Monday, August 13th was one of those indelible days you hope you don't have to have again.  I was at work and received an unexpected email from Dr. Shoffner with Spencer's muscle biopsy results.  The results were conclusive that there is mitochondrial dysfunction.

 Although based on everything that was done so far and from our initial consult with Dr. Shoffner, it was pretty certain he had some form of mitochondrial disease, there was still a chance in my mind that he was OK. Those thoughts came to an abrupt and unexpected end Monday afternoon.  All I could do was weep!  I tried to put myself in his shoes and imagine how he was going to feel.  He had told me several times that he felt there was nothing wrong with him.  I thought to myself, now I have 3 children with mitochondrial disease!  The self-pity and why me were going crazy.

Mitochondrial disease is a complex and difficult diagnosis but it involves clinical manifestations, laboratory data from blood, urine, and cerebral spinal fluid, mitochondrial analysis from a  muscle biopsy, and most important and most difficult is finding the gene responsible for the dysfunction.

The following is a quote from Dr. Shoffner:  "Mitochondrial diseases encompass a broad range of phenotypes ranging from neurometabolic diseases to certain cancers.  Clinical manifestations range from a single affected tissue to multi-organ disorders.  Symptom onset can occur at essentially any age and has the following patterns: 1. congenital onset; 2. Slowly progressive onset at any time during life; 3. Acute/subacute onset at any time during life" 

When Becky, Seth, and I returned from his initial appointment with Dr. Shoffner in Atlanta in December 2010, we had a family meeting to discuss with our children what was going on with Seth and that his prognosis was uncertain and poor.  It just so happened that a couple of weeks prior to this, Seth made a boat at pre-school.  The boat was made from paper cut out from colored paper and glued onto a larger white piece of paper.  The boat had a large sail.  The boat is framed and on one of the walls of our home.  This boat is very special and has significant meaning to our family.  This boat is our Pequod and is shown below.

Our Symbolic Boat--The Pequod

During this family meeting, I explained to my children that our family is on a journey and our method of travel is a boat or a ship.  Becky and I are the co-captains of this ship and all of our children were shipmates with each of us having very important responsibilities.   Our map was the scriptures and our compass or GPS was our Heavenly Father.  Our destination was unknown.  Our length of travel was unknown. The difficulty of the journey was unknown.  The conditions of the sea were unknown.

The only knowns were we had love that bonded us together which was stronger than the fear of the unknown future and territory that was ahead.  We had a map that was 100% accurate and the compass/GPS was completely reliable.  If we were to utilize theses tools, we would arrive at our destination.

My children are familiar with many stories of ancient ship travel including Christopher Columbus, Jonah, Lehi, and Jesus.  Jesus, after a long day of service, got into a boat to cross to the other side of the Sea of Galilee.  As they were traveling across the water, Jesus slept on a "pillow" while there was a "great tempest".  The boat was filling up with water and Jesus was still crashed out on his pillow.  The disciples were fearful of their very life and woke Jesus up and asked him: "carest thou not that we perish".  He spoke saying: "peace be still" and suddenly "there was a great calm". Matt 8:23-27,  Mark 4:36-41 

Sea of Galilee 1999

It also so happened that at this time, I was reading Moby Dick, by Herman Melville.   This great American novel about the Pequod whaling ship and its captain, Captain Ahab, who's life is full of shame, anger, and fear as Ahab sets out on a whaling voyage to find and kill Moby Dick, the Great White Whale who in an earlier voyage  bit off Ahab's leg and destroyed his ship.  Ishmael, the narrator, decides to go on this voyage to deal with his own depression, shame and fear. 

Our current situation and the uncertainty of it and comparing it to a journey on the water seemed to fit. My children understood the analogy and were on board as mariners and shipmates.   

What was not expected on this maritime voyage at that time was my other children would also be affected by mitochondrial dysfunction.  As unpredictable as mitochondrial disease is, it was also a complete shock and unpredictable that my boy Spencer would come down with this disease.   Sadness, grief, sorrow, anguish, distress, fear, lamenting describe to some degree my feelings, but I really cannot find the words to express how I truly feel.  Spencer and I have been mountain biking together since he was 6.  We have back packed together multiple times.  Recently, we have started road cycling and trail running together.  To have that taken away from us now really hurts!  

Spencer Tour of White Mountains 2011 Podium Finish

It is bad enough to have one child with an illness that is chronic, incurable, and not treatable.  To have 3 children now effected with this insidious disease is inapprehensible.  Life has been a struggle each day.  As I look back over the last several months and the challenges we've all faced, one thing I can say is I have the best co-captain in this journey that you can get.  Not only is her physical appearance beautiful, but inside she is golden.  She is strong and determined where I am weak.  I thank God daily for Becky.  

The other unexpected part of this journey is Sydney.  She is turning 18 in 2 months and it has been recommended by several of her doctors and teachers that we obtain gaurdianship/conservatorship over her.  You never expect this and it is impossible to prepare yourself for this.  As you watch your children grow up, you fully expect when they turn 18 that they will be physically, mentally, emotionally, and spiritually prepared to live on their own.  You don't expect to hire an attorney to make your case before a judge that your daughter in incapable of making decisions for herself.  We have been to multiple family events this past summer.  It has been very difficult listening to her cousins and friends speak of their post-high school plans.  When we spoke with her about getting guardianship over her, for the first time, she had some insight into her illnesses.  She cried as Becky and I sat on her bed.  "Why can't I be normal, I hate this disease, I hate taking all these pills, I just want to be normal like the other girls my age".  What do you say to those questions?  We just held her, cried with her, and told her we loved her.

Pacific Ocean, Monterey, California July 2012


As our family has been on our boat, I can relate to the feelings of the disciples--especially the feeling of fear. I long for the feelings of peace and calm. How does one experience these feelings when the tempest is relentless?  Oh how this most recent leg of our journey has been difficult. I wish the storm would pass and we could have some smooth sailing for awhile.  It seems that the post I wrote on Overcoming Adversity came from someone elses mind.

The text to the hymn "Master, the Tempest Is Raging" by Mary Ann Baker seem appropriate today. I have only included the second verse.  The third verse does not apply at this time--hopefully soon.

Master, the tempest is raging! the billows are tossing high!
The ski is o'ershadowed with blackness. No shelter or help is nigh.
Carest thou not that we perish? How canst thou lie asleep.
When each moment so madly is threatning. A grave in the angry deep.

Master, with anguish of spirit I bow in my grief today.
The depths of my sad heart are troubled. Oh, waken and save, I pray!
Torrents of sin and of anguish sweep o'er my sinking soul,
And I perish! I perish! dear Master. Oh, hasten and take control!