Science – Genetics – Genome – Research

DNA

 

There are 4,000 known rare diseases in the world. Only 250 have known treatments or cures. How can science move faster to develop much-needed treatments and cures?

I may not have paid as much attention to this question and the possible answer 5 years ago. Now it is the question that sits in my mind and demands my attention day-to-day, moment to moment. Can we find a cure for Kate’s rare form of mitochondrial disease? What would it take to find a cure? Is there an orphan drug out there somewhere that would fix/correct the breakdown in the protein synthesis chain of the one gene in her body affecting her mitochondria from doing their job of creating energy so that she can live?

This recent TED TAlk from Dr.Francis Collins, Director of the National Institute of Health (NIH) gives some insight into how the human genome and recent advances in science may unlock the key to treatments for rare disease. What is needed now is the will.

Will = money, resources, engaged and motivated scientists, motivated pharmaceutical companies, flexible government policy.

http://www.ted.com/talks/francis_collins_we_need_better_drugs_now.html

 

In Canada, our recent federal budget just announced $150 million dollars in funding for projects in genomics and personalized health, a Genome Canada-Canadian Institutes of Health Research (CIHR) partnership.

Of particular interest to our family is that Dr.Kim Boycott, a CHEO neuro-geneticist, will lead the enhanced Care for Rare genetic diseases in Canada program. This program is a continuation of FORGE, the first comprehensive genetics research program to identify rare/novel disease in children across Canada. Kate was part of the FORGE program, and it is a credit to the research of Dr.Boycott and her colleagues, as well as our metabolics doctor (Dr.C) that Kate’s disease was finally identified.

Genetics, a few months of my Grade 12 science class and first year biology program at University. Who knew that the science of genes and their variations would play such an important role in our life.

 

Julie

 

 

 

In Honour of Rare Disease Day

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Since starting this blog, and over the past few months, I have been telling you Kate’s story – her medical journey as a ‘typical’ newborn, to an unwell infant, to a severely chronically unwell toddler and preschooler who has undergone intensive and extensive medical investigation and inquiry. I’ve shared with you some of the details of the first 2 years of Kate’s life. The unbelievable stress, worry and outright and absolute fear that Kate would succumb to her disease or suffer even more irreparable harm. It drove us. It drove me. I became Kate’s most intense medical advocate and researcher. I was determined to find out what was ‘wrong’ with my child.

After our visit to the Mayo Clinic, it became very clear to me that what Kate was suffering from would not be easy to solve. I had been told before by more than one of her specialists that it was quite likely we would “never have a diagnosis for Kate”. This opinion was presented to me as almost normal – just a run of the mill medical opinion. In my mind, I rejected it outright. I would find out what was causing my child to be so unwell and to suffer so much. I would find out what was wrong and I would help her. I would find out what was hurting her and I would find a way to treat it – at the least, or cure it – at the best. I would do that for her, and I was going to find the right people to help me.

Since our first days of intensive medical investigation with Kate, we have accumulated a spectacular team of no less than 7 different medical centers: CHEO, Sick Kids, the Mayo Clinic and the NIH Rare and Undiagnosed Disease Program, Texas Baylor University, and research facilities at McMaster Health Sciences Centre, Boston Medical Centre, and more, and we have more than 30 different medical specialists for her. While she is monitored regularly by all of them, she is monitored very closely by a few – and I count these closest physicians to Kate as some of my strongest allies. I have developed strong relationships with them. I have learned how to speak their language, and how to adjust for their different communication/medical delivery styles. I feel like we are part of an integral team, moving in one direction to solve an incredibly daunting question. What is making Kate so sick?

Over the first four years of Kate’s life she was investigated for more than 20 different known conditions. Twenty.

 

Some Facts About Rare Diseases:

  • 1 million Canadians suffer from a rare disease – this is 1 in 12.
  • 80% (500,000) are children
  • There are approximately 7,000 rare diseases.  About 50% of those are unknown.
  • There is diagnostic testing for only 150 rare diseases.
  • 25% of rare diseases take between 5 to 30 years to diagnose accurately.
  • 40% of rare disease sufferers have a wrong diagnosis
  • 50-70% never receive a diagnosis
  • The average cost of the ‘diagnostic odyssey’ for most rare diseases is $23,000 (Kate’s diagnostic odyssey was upwards of $100,000)

 

This past June, as part of my ongoing medical file on Kate, I created a ‘disease consideration pathway’ as I call it to help describe the testing that Kate had undergone over the course of her medical odyssey. These were the tests and conditions that I had made note of and could recall. I know there were more (less plausible in the end), and with every test, I hoped,  I truly secretly hoped that this would be it, this would be the disease and we could move forward toward treatment and a cure. Even after googling some of these conditions and understanding what ‘having’ them would mean for Kate, I still just wanted to know.

Kate’s tests involved many rare diseases that had ‘known’ genes. Therefore we could genetically test her for them. The tests for each of these conditions involved single gene testing and took weeks/months to complete and receive the answer back.

In the fall of 2010, when Kate was three, we agreed to a genetic research project that was going to do ‘genetic mapping’ and sequence all of Kate’s genes. A MitoCarta, or mitochondrial map had been developed, and it was theorized that the genetics team would map any genetic variants that might impact on the functioning of the mitochondrion or mitochondrial process. Unbeknownst to us, the project fell through.

In the spring of 2011, we signed on to a second project that would again identify genes for inherited disorders and congenital anomalies. The principal investigator was a neuro-geneticist from CHEO and the University of Ottawa who would be conducting genetic exome sequencing. Using a process called Next Generation Sequencing, she would be able to examine all 22,000 coding genes in a short time period (2 weeks), for a fraction of the cost required to test one gene at a time.

As I read through the consent form for this study we had agreed to be a part of, I remember how I felt when we signed the form. It was yet more paper to sign. It was yet another study to try to find out what was happening to Kate. I wouldn’t say I had lost hope, but I felt a certain amount of apathy at yet another test that would quite likely bring us no concrete information. But this time it would be different. Kate had become part of the FORGE study.

FORGE (Finding of Rare Disease Genes in Canada) was an incredible consortium style research project that created an extensive network of physicians and research scientists across Canada who would have access to next-generation sequencing in order to identify rare genetic diseases for many undiagnosed Canadians.

For several months I had put this genetic testing out of mind. We carried on caring for Kate, dealing with her multiple conditions, regular hospital visits, and hospital admissions. But then, in the early fall of September 2011 we received a phone call from our metabolics doctor. They had found something ‘provocative’ and wanted to further investigate. Details were not discussed with us, but we were asked to come in for bloodwork – all of us. And then we waited again.

Several weeks later, on November 13th 2011, we met with Kate’s metabolic doctor. He started to explain the type of testing that had been done and what they had found. They had identified Kate’s disease.

For me, there was a brief flash – a moment of euphoria – they had found it and now they could help her. And the moment passed quickly and our world – Kate’s world changed forever. This was a “novel” disease – a new and rare condition – so rare that Kate was the only known case in the world.

N=1

The specific genetic anomaly for Kate was an exact match to a recessive anomaly that both Brian had on the same gene. Being recessive, we did not ‘have’ the disease and have no symptoms, but our children would have a 1 in 4 chance of inheriting this recessive genetic disease. The extreme rarity of this occurrence could barely be quantified. Kate was literally 1 in 7 billion.

It wasn’t comparable to anything. It wasn’t understandable.

We left that meeting in a state of shock. I’m not sure I heard much else after hearing that Kate had an unknown/novel disease that no one else in the world had. I felt numb.

We went from the isolation of having a medically fragile and medically complex child with an undiagnosed disease, to having a child diagnosed with a disease so rare she was the only one in the world (that we knew of) suffering from it.

Where did we go next? What was the next step? Both of those questions were front and center for me, but I can’t remember asking them at that time.

 

As I read back on the consent form for the FORGE study, the following excerpt on page 3 grabs my attention:

Are There Any Possible Benefits?

“You may or may not benefit from participating in this study, however we hope that the information gained for this study will help doctors treat patients in the future”.

 

 

Julie

A Little Pot of Yeast

Last week I had an opportunity to visit the Research Institute of the Children’s Hospital of Eastern Ontario (CHEO) to meet the team who have been working on Kate’s rare recessive genetic disease. This was a highly anticipated day as the research into Kate’s disease has gone on ‘behind the scenes’, but is so important to us as a family. What was extra special to the dedicated team of scientists working on Kate’s disease, was the opportunity for them to meet her. These are not ‘frontline’ doctors. They don’t work in the ER, in the clinics, or on the in-patient floors interacting with families and getting to meet the children whose lives they impact so incredibly. For them, meeting Kate was a pretty great moment.

 

The amazing researchers working on Kate's genetic anamoly. Searching for a cure. We love these scientists!

The amazing researchers working on Kate’s genetic anomaly. Searching for a cure. We love these scientists!

 

As I’ve described before in previous posts, Kate was the first person in the world diagnosed with a rare recessive genetic mitochondrial disease. The disease has caused a mutation of one gene responsible for mitochondrion functioning. We’ve been asked not to share the name of the gene as the first ever research and clinical description for this newly discovered disease is still pending medical journal publication. (Man, I can’t wait to share that with all of you!)

Through collaborative research with researchers in the United Kingdom and Boston, USA, there are now 10 known cases of this disease worldwide over the last 20 years of available data. This is a childhood disease, that is progressive and life limiting. Kate is 1 of 4 children alive today with this disease.

There is currently no known treatment or cure for Kate’s disease, which means her physicians are only able to practise cautious monitoring of her condition and management of her chronic and acute symptoms.

BUT….

CHEO is working hard to change this for Kate by conducting incredible research and collaborating with the international team of doctors and research scientists working on this disease. They are trying to find the cause of the protein deficiency which leads to reduced mitochondrion functioning in Kate. They want to cure her disease.

They are using yeast as the ‘vehicle’ in which to implant Kate’s one gene mutation. Yeast is interesting as it can grow with either both strands of DNA, or only one (we as humans – and most living beings – need both sets in order to grow). So Kate’s research team can isolate the one gene and study its mutation more directly.

My little girl. A little pot of yeast.

My little girl. A little pot of yeast.

When they have that figured out, they’ll move on to her skin cells and examine the one genetic mutation and how it interacts with all of the genes in Kate’s DNA. It is super-scientific stuff, and I am really not doing it justice in describing it to you. I’m also be cautious about sharing too much (cat out of the bag and all that….).  Really incredible. And it will change the lives of many more people than Kate as they are establishing a bio-repository of the knowledge they are gaining by researching Kate’s rare disease.

 

A repository of yeast being built by examining Kate's disease.

A repository of yeast being built by examining Kate’s disease.

To look at your child’s disease from under a fume hood, being grown in a petri dish is pretty incredible. It was a moment.

This month I am practising being thankful. I am thankful for Dr.H and his team at the CHEO RIT for all of their incredible work.

 

And a shout out to #whatifhc

What if laboratory researchers and scientists had the opportunity to meet the families and patients whose lives they are saving?

 

Julie

Mayo Clinic Visit – Part 3

The end of our long week at the Mayo Clinic in Rochester Minnesota was coming to an end. There were still many conversations to have and specialists to meet. Kate was doing well. Her stamina was good, but she had a vomiting episode one night that had me worried we might start an episode while on our visit there. Thankfully that did not happen – though perhaps it may have led to more insight into her condition (?)
For a 2-year-old child, Kate handled the visit well. We still had to contend with entertaining her in waiting rooms, and ‘wrangle’ her during our meetings with specialists. Of course she had to be present – after all, this was all about her – but it would have been so much easier and less distracting to have her out of the room. In fact, in a few situations, my mom would leave the room with Kate and take her for a walk.

October 26th, 2009
We were having our second, and more in-depth meeting with medical metabolics, Dr.Gavrilova. She reviewed with us her impression of Kate’s history combined with test results such as recent bloodwork, and the muscle biopsy specimen from CHEO. She felt all symptoms pointed to mitochondrial disease.

As I have suggested before, being told you have mito is like being told you have cancer. There is incredible variability and severity in the disease. Some present as mild – and treatable/manageable, while other forms of the disease will undoubtedly result in death. Mito can strike many different organs and systems of the body – or multiple systems at the same time. It also strikes children and adults (i.e. it is not always a childhood disease).

For Kate, there was no specific amino acid abnormality that could be found – all were high. In the case of specific disease presentation for mito, if there are 2 or 3 high (for example), that helps to point to, or specify, a particular type of disease.

We discussed the testing that had been done by and/or coordinated by CHEO. Their testing had been extensive and has covered almost all the bases. Kate’s blood and muscle tissue had been sent to the McMaster University Health Sciences Centre, Baylor University in Texas, Columbia University, Boston etc.

Further, Dr.Gavrilova felt that if Kate had a form of mitochondrial disease she appeared to be on a milder form of the spectrum.
I found this an interesting comment/assumption this doctor how had not studied Kate extensively, nor had she done any of the primary testing or analysis of Kate. Further, she did not have a concrete diagnosis for Kate – so how could she make this assumption? I filed the comment in the “general comments” section of ongoing file in my mind re: Kate.

In discussing Kate, she described how her lactate were around 2.7, i.e. within normal range, but had been in the high range during her episodes. Elevated lactate is a typical symptom of mitochondrial disease. However, Kate’s muscle enzymes were fine, and there was no specific pattern to her symptoms that suggest a specific type of mito.

There are some well documented forms of mito that are described in the literature: MELAS, MERFF, MNGIE, Leigh’s syndrome etc. that have specific presentations of a cluster of symptoms and can be tested for via genetic/blood test.

Dr.Gavrilova also suggested that Kate undergo a second muscle biopsy and that a fresh sample of tissue should be analyzed – rather than frozen first as we the case in the first sample.

 

Dr.Mack – Neurology

This was our third visit to neurology at Mayo and our second with Dr.Kenneth Mack, who had appeared to have taken a keen interest in Kate. He was very well prepared with knowledge of her history and keen to help us sort out how to manage Kate more effectively in the absence of a diagnosis – though he did weigh in on that front as well.

I wanted to discuss pain management with Dr.Mack. Kate had a significant amount of pain with her episodes. Something I felt so deeply painful as a mom since her pain was not managed well. It is a caution to other parents with young, non-verbal, developmentally delayed children. They cry when they are in pain or distress, they have no other way of expressing it. And in my opinion, they are not ignored but they are also not assessed and treated as quickly as someone crying out with words. “Children cry” seems to be the understanding and to me – it appears it delays any intervention.

I feel like doctors are used to children crying and that this does not always call them to action. I felt so strongly about advocating for Kate’s pain management I did extensive reading on it for non-verbal children. I eventually sought out the pain management team at CHEO to assist me in assessing and treating Kate. What I found most distressing was working with teams of residents and doctors who did not know Kate who would take a very slow and  controlled approach to administering pain medication. I can recall one visit where Kate was clearly in pain, I asked the nurse to get me the resident. When the junior resident came in and I described what I felt I was seeing and my request for morphine for Kate (which what we were using at the time), she said she would need to consult the ‘senior’ (senior resident). She was gone for more than 20 minutes. Now let me pause her and ask you – would you wait 20 minutes for pain management to even be assessed let alone administered? No – neither would I. I did not let Kate wait either, I called the on-call pain management doctor who arrived at Kate’s bedside before the senior resident did. He prescribed morphine for Kate.
This is the difficult of pain management in young children. I am grateful that I know what to do and who to call, and I realize the assessment for Kate is made more difficult because her lack of case coordination at that time. But to watch you child cry out, to writhe around in her bed, to look at you with pleading eyes, and to eventually give up – it is absolutely heart wrenching and it should not happen.

So, I was keen to talk to Dr.Mack about what he would suggest. Tylenol and Advil combined sometimes worked for Kate. Other times we needed to move to morphine (which made me nervous) which worked well. Interestingly Dr.Mack suggested that morphine did not work well for migraine variant syndrome – which he felt was the underlying cause of Kate’s cyclical vomiting. He suggested instead a Tylenol suppository (if Kate was vomiting) combined with anti-nauseants such as Phernegen. He was also a strong advocate of IV hydration at the onset of symptoms. To this day IV hydration is the first and most important part of Kate’s protocol when she has an episode. 

Dr. Mack advocated again to re-try amytryptiline with Kate. He said that in 90% of cases of cyclical vomiting syndrome it works. He suggested we needed to try this drug longer (we had tried it before) and at a higher dose (which we would have to build up to). He counselled me to do further reading at the American Council on Headache Education.

I then asked the question that burns in my brain (do you know what is wrong with my daughter). If this wasn’t mitochondrial disease, what would it be?

Dr. Mack replied that the top 10 choices for Kate was that this was some form of mitochondrial disease – perhaps a phenotype of one of the known mito diseases – but that we may never have a confirmed diagnosis. He called Kate’s mito disease a ‘working diagnosis’.

(A “phenotype” is basically like saying it waddles, quacks, looks like, has webbed feet, a bill, feathers etc. etc. like a Duck..but we can’t confirm it is a duck).

 

Could it be this duck?

Could it be this duck?

Or is it this duck?

Or is it this duck?

 

Dr.Mack also broached the topic of the “mito cocktail” a very popular cocktail of supplements that supposedly helped to manage and/or alleviate the symptoms of mitochondrial disease. There had been much debate among Kate’s doctors about starting the cocktail and about its effectiveness. We had been counselled so far to not go ahead with it as there was still too much uncertainty about Kate’s disease and the benefits, but also the problems of starting on the mito cocktail. Further, the research and science was very limited with much of the evidence being anecdotal. Still, her was a Mayo clinic neurologist advocating that we may want to try it with Kate. It was certainly a conversation I would try to have with Kate’s CHEO doctors again.

Dr. Mack reviewed a few other questions we had such as:

– What about Kate’s chronic constipation?
A non issue for Dr. Mack and certainly not the cause of her episodes, though constipation would become worse with dehydration.

– Were vaccinations safe:
For the most part yes. But part of the pertussis vaccinations is typically withheld in mito-kids.

This was our last visit with Dr.Mack and at the end of it he handed his business card asking us to stay in touch and to feel free to follow-up with him if we had any further questions. Though to this day I haven’t been back in touch with Dr.Mack, I have a strong respect for him and think of him as part of Kate’s broader medical team.

 

Dr.Rodriguez – Hematology

We had met with Dr.Rodriguez at the beginning of our visit to Mayo, but as she did not have all the lab specimens and information about Kate, we had rescheduled our visit for later in the week.

Dr. Rodriguez reviewed with us what we already knew about Kate’s red blood cells (RBCs). She was producing them, but they were small (microcytic), pale (not red, but a pale pink), and misshapen. This would impact Kate’s ability to utilize/metabolize iron properly (i.e. she has iron, she just can’t use it). This is why a ‘sideroblast’ or ring of iron forms.

Dr.Rodriguez felt that there was really no intervention they could do other than watch and monitor. Kate’s Hbg did not drop below the low 70s and would rebound to the low 90s – neither level required transfusion (120 would be normal). She felt Kate’s sideroblastic anemia was a ‘anemia of chronic disease’.  She felt that if Kate’s episodes became less and less, her Hbg may normalize. She described this a function of Kate’s bone marrow, which is an organ of the body and mirrors how the body is feeling. Kate’s RBC could not normalize because of her illness.

Dr.Rodriguez did not have a suggestion of an underlying illness for Kate.
We now know that it is a key feature/condition of Kate’s rare form of mitochondrial disease.

 

And that concluded our visit to Mayo. Seven days of intense medical discussions about my daughter. Hoping for answers.

What I did come away with was a renewed confidence that our children’s hospital had been doing an excellent job for Kate – from a diagnostic point of view. Their suspicions of mitochondrial disease were confirmed and they were on the right path with testing.

What we did not come away with were clear answers or a new direction. And in the end, perhaps the visit was not necessary, but it give me the confidence that we were starting to exhaust all channels in hoping for a diagnosis for Kate. The visit to Mayo may not have been a ‘success’ when it came to answers, but in the bigger picture it was a necessary step.

 

Julie

 

 

 

Mayo Clinic – The Visit Part 2

The continued story of our visit to the Mayo Clinic.

October 23rd
We started our long day with a visit to metabolics. A detailed history was taken and we reviewed the family genetic history that I had provided a couple of days before. There was much discussion and review of Kate’s “episodes” and detailing what exactly occurs. We discussed specifics such as Kate’s blood lactate, muscle biopsy and results, and carnitine levels etc. I am still amazed at the amount of medical information and detail I carry around with me in my head. Details memorized and complicated medical jargon understood and able to be discussed as needed. (Where did I put that MD diploma?).
The metabolics resident – yes, we met with a resident first – was very interested in Kate’s sensory neural hearing loss, developmental delay, sideroblastic anemia and her episodes. She felt they are clearly pointed to a metabolic disorder. Again, this was not news to us, but good to hear from yet another source.
Something that was explained to us that I did not fully appreciate were the muscle biopsy results. Kate’s results were coming back negative for mitochondrial disease. In brief, she had many mitochondrion in the muscle and they are appeared to be healthy/normal. What was explained to us at the Mayo Clinic is that the tissue biopsy needs to come from affected muscle and/or the brain. A negative result can simply mean that tissue is not affected – at that time. As I have said before, mitochondrial disease can be a bitch to diagnose.

A Lesson on Mito
I got an extensive biology lesson at Mayo about mitochondrial disease:
– in kids the more common causes of mitochondrial disease are the nuclear genes (maternal DNA)
– mito is very difficult to diagnose (better now in 2013)
– not all mitochondrial diseases cause increase lactic acid in the blood or prolonged elevated blood lactate
– not all tissue are affected, e.g. in Kate her muscle tissue of the large rectis femoris leg muscle may not yet be affected, while other areas of her body are
– additional tests can be run on Kate’s tissue samples including; DNA deletion sequencing (I thought we had done that), expanded muscle tissue analysis (seems vague), and an EEG when she is having an episode.

We left this first meeting with metabolics feeling no more informed, but interested in what their attending physician would have to say once Kate’s muscle biopsy tissue arrived from Canada and was analyzed. Something that had not been sent in advance.

Our second meeting that day was with Dr.Mack from neurology.
Dr.Mack had reviewed the detailed information provided to his resident and had asked to meet with us again as our last meeting was cut short due to a long day for Kate.
Dr.Mack was convinced that Kate’s ‘episodes’ were episodes of cyclical vomiting syndrome. He felt that a drug cocktail would be able to slow/stop the episodes or at the least reduce their intensity. He proposed Amitryptiline and Riboflavin. He expected episodes to reduce in frequency and intensity and if not – then an extensive GI workup should be done.
Dr.Mack described to us how cyclical vomiting can be common as a stand alone condition at this stage/age in children, and it could be they way mitochondrial disease was presenting. He further described how it could be severe enough to last several days and require hospitalization as had been our experience to date. Though Kate had been prescribed amytriptyline before – Dr.Mack felt the dosage needed to be much higher which would require ‘ramping’ up the dosage over time and watching carefully for side effects such as; increased appetite, listlessness, prolonged QT on EKG.
I was skeptical about amytriptyline. Though cyclical vomiting syndrome seemed to fit for Kate, we had tried amytriptyline before and found Kate had side effects that were disconcerting for us; loss of balance, frequent falls, listlessness. I was not keen to try the drug again – but since it was being recommended by another neurologist (from Mayo), I felt like we should.

We also discussed with Dr.Mack Kate’s global developmental delay and her progression. There had been little information about Kate’s brain myelination pattern since her first MRI at the age of 12 months. A subsequent MRI showed little to no change and the information itself was not a diagnosis or a condition, it was simply a fact that Kate’s white matter was developing slowly and perhaps not creating the neural synapses her brain required to carry information from one area to another. Further, there can be no prediction on development with only this information, and there was nothing more we could find to describe Kate’s developmental delay. Dr.Mack was clear with us that Kate’s delayed myelination pattern was not causing her developmental delay, but that it was part of the bigger picture of Kate’s condition. As for a prediction for development we should look at the near past (3-6 months) as a prediction for how her development will progress. The long-term can’t be predicted with any accuracy.

And then we heard the words again, Mito is very difficult to diagnose, though with Kate’s clinical picture it is the top of the list.

You know what that makes me think of everytime I heard it…this…

What to expect when you expect mitochondrial disease.

What to expect when you expect mitochondrial disease.

 

Later that afternoon we were to meet with Dr.Lloyd, the coordinating pediatrician at the Mayo Clinic to have a ‘touching base’ meeting to discuss how our visit was going and any concerns we might have. I made a list to discuss at the meeting:

1. What is an appropriate protocol for Kate when she has an episode? i.e. at the ED
2. What other medical conditions can we expect Kate to develop?
3. Vaccines – are they safe for Kate? Should she follow the regular schedule
4. Can we review the step metabolics (at Mayo) are taking to diagnose Kate, e.g. deletion profile, mito DNA and nuclear DNA etc.
5. What is the working diagnosis for Kate?
6. Where can we find reliable, scientific information on mitochondrial disease (diagnosis, treatment, description)
7. What is the difference between a metabolic disorder and mitochondrial disease?
8. Discuss the proposed GI tests and the importance of doing them (i.e. neurology thought we should wait and go step by step)
9. Bloodwork results, bone marrow biopsy slides, muscle biopsy slides (have they arrived from Ottawa)?
10. What is the risk that Kate might suffer a catastrophic event due to this disease. Is there a spectrum?

 

 

Julie