Mitochondrial 101 What happens when the battery runs low? Kristi - - PowerPoint PPT Presentation

Mitochondrial 101

What happens when the battery runs low? Kristi Wees MS Chemistry Medical Advocate www.EmpoweredAdvocacy.com

How I came to learn about Mitochondrial Disease…

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A personal journey involving my youngest child’s health

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Around 12-15 month she started to exhibit “autistic like symptoms”

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When she was around 18 months old Mitochondrial disease was mentioned to us for the first time as a possible diagnosis.

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She is now 7 years old and doing very well, in a regular classroom with no need for an IEP .

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We have learned volumes about health and disease on this journey.

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I now hope to help other families navigate to improved quality of life for their children, through my business Empowered Medical Advocacy.

What are mitochondria? What do they do?

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Mitochondria are the Powerhouses, engines or batteries of your cells, produce 90% of energy needed to function

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They convert FOOD nutrients to ENERGY

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High energy demand systems may be impacted first- heart, brain, GI, muscles, and lungs

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Estimated that 1 in 4000 or possibly 1 in 2000 are affected by mitochondrial disease.

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Research shows 1 in 200 of us carry a genetic mutation that could develop into mito in their lifetime.

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Red flags: 3 or more organ systems involved

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For many of our kids- GI, neurologic, immune

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Video

Source: Crayola.com

Symptoms of Mitochondrial Disease

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Poor growth

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Loss of muscle coordination, muscle weakness

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Neurological problems, seizures

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Autism, autistic spectrum, autistic-like features

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Visual and/or hearing problems

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Developmental delays, learning disabilities

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Heart, liver or kidney disease

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Gastrointestinal disorders, severe constipation

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Diabetes

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Increased risk of infection

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Thyroid and/or adrenal dysfunction

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Autonomic dysfunction

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Neuropsychological changes characterized by confusion, disorientation, and memory loss.

Source: Mitoaction.com

Disease versus Dysfunction

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Disease= mutation (only detected in 50-60% of individuals)

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Dysfunction= clinical features but no genetic mutation found (at this time)

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“Mitochondrial dysfunction generally refers to mitochondria that are impaired in function but not severely impaired enough to fulfill the criteria necessary for the diagnosis of mitochondrial disease. In essence, mitochondrial disease can be thought of as a severe form of mitochondrial dysfunction, and mitochondrial dysfunction can be thought of as a less severe form of mitochondrial disease.

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If mitochondrial dysfunction can be represented by an engine that is sputtering, mitochondrial disease would be represented by an engine that is constantly in the repair shop.” – Dr. Rossignol and Dr. Frye Autism Science Digest

Mitochondrial Disease Criteria

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Walker Criteria (1996)

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Nijmegen Center for Mitochondrial Disorders scoring system (2001)

u http://mitochondrialdiseases.org/fmm/docs/CLINICAL%20CRITERIA.pdf

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Modified Walker Criteria (2002, Bernier)

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Morava criteria (2006) Figure 2

u http://www.tacanow.org/wp-content/uploads/2013/05/Mitochondrial-Dysfunction-

ASD-1.pdf

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Mitochondrial Medicine Society (2015)

What Causes Mitochondrial Disease?

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Genetics- nuclear and mitochondrial DNA mutations (Primary Mitochondrial Disease)

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Environmental toxins (Acquired Mitochondrial Disease or Secondary Mitochondrial Disease/Dysfunction)

u “For many patients, mitochondrial disease is an inherited genetic condition. An

uncertain percentage of patients acquire symptoms due to other factors, including mitochondrial toxins.” -Mitoaction website

u “Medicines or other toxic substances can trigger mitochondrial disease.” –

Mitoaction website

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Other medical conditions and other genetic disorders (Secondary Mitochondrial Disease/Dysfunction) Source: Mitoaction.org

Genetics

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Two types of DNA “genes” in our bodies…

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Nuclear DNA= nDNA

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Found in the Nucleus of the cell

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Over 1500 nuclear genes impact the functioning of the mitochondria

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“In the pediatric population, autosomal recessive inheritance of nuclear genes is the most common etiology . 75-90% of kids, who have these disorders, have inherited an altered gene, one from mom and one from dad and that results in their disease process” –Dr. Fran Kendall

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Mitochondrial DNA= mtDNA

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Maternally inherited

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37 genes

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Found in mitochondria (not in the nucleus)

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Heteroplasmy - mixture of mutated and non mutated mtDNA, increased % of this influences severity of disease.

Source:http://mitochondrialevehypothesis.weebly.com/nuclear-dna-v-mtdna.html

Where is Mito?

Source: www.foundmm.org Source: www.amdf.org.au Where does Mitochondrial Disease hide?

History of Mitochondrial Disease and Autism

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Olivera, Portugal (2005) Mitochondrial dysfunction in autism spectrum disorders: a population-based study.

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Five of 11 patients studied were classified with definite mitochondrial respiratory chain disorder, suggesting that this might be one

• f the most common disorders associated with autism (5 of 69; 7.2%) and warranting further investigation.

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Hannah Poling “Vaccine Court” Case (2008) and Journal article (2006) Developmental regression and mitochondrial dysfunction in a child with autism.

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(2008) Mitochondrial disease in autism spectrum disorder patients: a cohort analysis.

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Although all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism.

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• Dr. Richard Kelley Manuscript (2009) Evaluation and Treatment of Patients with Autism and Mitochondrial Disease

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Shoffner (2010) Fever plus mitochondrial disease could be risk factors for autistic regression.

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Autistic regression occurred in 60.7% (17 of 28), a statistically significant increase over the general autistic spectrum disorder population (P < .0001). Of the 17 individuals with autistic regression, 70.6% (12 of 17) regressed with fever and 29.4% (5 of 17) regressed without identifiable linkage to fever or vaccinations. None showed regression with vaccination unless a febrile response was present.

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JAMA article (2010) Journal of American Medical Association December 1, 2010-Vol 304,No. 21

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Mitochondrial dysfunction may influence processes highly dependent on energy, such as neurodevelopment, and contribute to

• Autism. In this exploratory study, children with Autism were more likely to have mitochondrial dysfunction, mtDNAoverreplication,

and mtDNA deletions than typically developing children.”

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Frye, Rossignol (2012) Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis.

Mito and Autism- 2012- today

• Dr. Richard Frye’s research

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“Most children (79%) who had ASD and mitochondrial disease did not have a genetic reason that could explain their mitochondrial dysfunction. Therefore, the mitochondrial problems reported in these children may have been due to a biochemical abnormality (termed secondary mitochondrial disease).”

u –Rossignol and Frye, Autism Science Digest and Mitochondrial dysfunction in

autism spectrum disorders: a systematic review and meta-analysis (2012)

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Treatments for biomedical abnormalities associated with autism spectrum

• disorder. (2014)

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Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome. (2015)

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Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder. (2015)

Acquired Mitochondrial Disease and Autism

What Autism Is and Isn’t

https://babyfoodsteps.wordpress.com/2012/07/27/what-autism-isnt/

MiTOXins and MiTOXiC substances

To read more about these go to: www.babyfoodsteps.com

Testing: To Biopsy or not to Biopsy

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For many years the “gold standard” of mitochondrial disease diagnosis was a muscle biopsy.

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Within the last 5 years, the field has shifted away from muscle biopsy to focus much more on genetic mutations and genetic testing.

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Some physicians still do muscle biopsy for confirmation, but the procedure can be invasive and there may be anesthesia risks if the child has mito, so exhausting all other less invasive testing, first, may be preferred.

Testing Basics…

Source: http://www.mitosoc.org/toolkit/

Possible Abnormal Results

To discuss with your specialist… Source: http://www.mitosoc.org/toolkit/

What if the testing is “normal”

Source: http://www.mitosoc.org/toolkit/

Additional Testing

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• Dr. Fran Kendall’s article in Autism Science Digest 2011 suggests Tier 1 and

Tier 2 testing: http://www.mitoaction.org/files/AutismOne2011.pdf

Additional Testing

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• Dr. Richard Frye’s paper

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Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder. Transl Psychiatry. 2013 Jan 22;3:e220. doi: 10.1038/tp.2012.143.

Genetic Testing

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Mitochondrial DNA testing (37 genes)

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Nuclear DNA testing for mitochondrial genes (1500+genes)

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Gene Panels for specific mitochondrial disorders (MELAS, MERF , Leigh’s, etc)

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Whole Exome sequencing (30-50% diagnosis rate)

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Direct to consumer testing: 23 and me

Where do I start as a concerned parent?

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Talk to your pediatrician- some may be aware of mitochondrial disease and some may need you to bring them some information to start the conversation.

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Review symptoms lists and criteria with your pediatrician and if mito is suspected, seek a specialist who can assist with testing.

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Specialists who know about mitochondrial disease tend to be in genetics or neurology departments.

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Educate yourself… Mitoaction’s Mito Autism Roadmap

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Connect with other parents on a similar journey through Facebook or support calls or in-person meetings.

So my child has mitochondrial dysfunction, Now what?

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Though it is said there is no cure for mitochondrial disease, there are ways to improve and optimize quality of life.

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Half of the treatment is being aware of and avoiding anything that will further impair the mitochondria (Mitoxins).

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The other half of treatment is providing the body all that it needs (nutrition, exercise, sleep, etc.) to maximize the energy it is producing.

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Mito cocktail- a combination of vitamins and minerals meant to nourish and support the mitochondria’s biochemical pathways. Every doctor has a different formula. One at a time.

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Every reaction, whether positive or negative, gives you insight into your child’s unique biochemistry. By understanding these reactions, you can best support your child’s health.

Some last thoughts...

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Diet and Lifestyle can have HUGE impacts (both positive and negative) on a child with mitochondrial disease or dysfunction.

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Unfortunately there is no “one size fits all” treatment or cure for each child that has mitochondrial disease or dysfunction, since their biochemical abnormality may be different than another child who also has mitochondrial

• disease. With that said though…a biochemically individual approach can be

implemented for each child that can lead to improved quality of life.

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Educating, Informing and Empowering yourself as a caregiver and parent along with building a TEAM of professionals around your child who listen and honor your input, feedback and preferences as a parent, are crucial to your child’s success.

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Listening to your gut instincts and trusting your knowledge about your child, are the keys to helping your child improve. You truly know your child best.

I am here to help in your journey

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Thank you for having me today!

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Through my company, I offer medical advocacy and navigation services to families who are looking for answers and improved quality of life for their child.

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You can contact me here: Kristi Wees, MS Chemistry Medical Advocate, Empowered Medical Advocacy www.EmpoweredAdvocacy.com kristi@empoweredadvocacy.com 724-613-2378

Additional Resources

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Resources available on www.EmpoweredAdvocacy.com/mitoresources

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Facebook group- Mitochondrial Autism and Autism Like Mito

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Alyssa Davi's 2 articles: mitoaction.org/autism

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Cristy Balcells book: Living Well with Mitochondrial Disease

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Mitoaction website and quarterly mito/autism support call- next call July 19th

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Epidemic Answers mitochondrial dysfunction page

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• Dr. Richard Kelley's manuscript

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Dr.Frye's papers available on pubmed and Autism File article (June 2016)

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• Dr. Fran Kendall's article on Mitochondrial disease and Autism

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Cleveland Clinic CME videos- Autism Spectrum Disorders: Research and Medical Treatment Implications