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… A personal journey involving my youngest child’s health u Around 12-15 month she started to exhibit “autistic like symptoms” u When she was around 18 months old Mitochondrial disease was mentioned to u us for the first time as a possible diagnosis. She is now 7 years old and doing very well, in a regular classroom with no u need for an IEP . We have learned volumes about health and disease on this journey. u I now hope to help other families navigate to improved quality of life for their u children, through my business Empowered Medical Advocacy.
What are mitochondria? What do they do? Mitochondria are the Powerhouses, engines or u batteries of your cells, produce 90% of energy needed to function They convert FOOD nutrients to ENERGY u High energy demand systems may be impacted u first- heart, brain, GI, muscles, and lungs Estimated that 1 in 4000 or possibly 1 in 2000 u are affected by mitochondrial disease. Research shows 1 in 200 of us carry a genetic u mutation that could develop into mito in their lifetime. Red flags: 3 or more organ systems involved u Source: Crayola.com For many of our kids- GI, neurologic, immune u Video u
Symptoms of Mitochondrial Disease Poor growth u Loss of muscle coordination, muscle weakness u Neurological problems, seizures u Autism, autistic spectrum, autistic-like features u Visual and/or hearing problems u Developmental delays, learning disabilities u Heart, liver or kidney disease u Gastrointestinal disorders, severe constipation u Diabetes u Increased risk of infection u Thyroid and/or adrenal dysfunction u Autonomic dysfunction u Neuropsychological changes characterized by confusion, disorientation, and memory loss. u Source: Mitoaction.com
Disease versus Dysfunction Disease= mutation (only detected in 50-60% of individuals) u Dysfunction= clinical features but no genetic mutation found (at this time) u “Mitochondrial dysfunction generally refers to mitochondria that are impaired u 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. If mitochondrial dysfunction can be represented by an engine that is u 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 Walker Criteria (1996) u Nijmegen Center for Mitochondrial Disorders scoring system (2001) u u http://mitochondrialdiseases.org/fmm/docs/CLINICAL%20CRITERIA.pdf Modified Walker Criteria (2002, Bernier) u Morava criteria (2006) Figure 2 u u http://www.tacanow.org/wp-content/uploads/2013/05/Mitochondrial-Dysfunction- ASD-1.pdf Mitochondrial Medicine Society (2015) u
What Causes Mitochondrial Disease? Genetics- nuclear and mitochondrial DNA mutations (Primary Mitochondrial u Disease) Environmental toxins (Acquired Mitochondrial Disease or Secondary u 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 Other medical conditions and other genetic disorders (Secondary u Mitochondrial Disease/Dysfunction) Source: Mitoaction.org
Genetics Two types of DNA “genes” in our bodies… u Nuclear DNA= nDNA u Found in the Nucleus of the cell u Over 1500 nuclear genes impact the functioning of the mitochondria u “In the pediatric population, autosomal recessive inheritance of nuclear genes is the u 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 Mitochondrial DNA= mtDNA u Maternally inherited u 37 genes u Found in mitochondria (not in the nucleus) u Heteroplasmy - mixture of mutated and non mutated mtDNA, increased % of this u influences severity of disease. Source:http://mitochondrialevehypothesis.weebly.com/nuclear-dna-v-mtdna.html
Where is Mito? Where does Mitochondrial Disease hide? Source: www.foundmm.org Source: www.amdf.org.au
History of Mitochondrial Disease and Autism Olivera, Portugal (2005) Mitochondrial dysfunction in autism spectrum disorders: a population-based study. u Five of 11 patients studied were classified with definite mitochondrial respiratory chain disorder, suggesting that this might be one u of the most common disorders associated with autism (5 of 69; 7.2%) and warranting further investigation. Hannah Poling “Vaccine Court” Case (2008) and Journal article (2006) Developmental regression and mitochondrial u dysfunction in a child with autism. (2008) Mitochondrial disease in autism spectrum disorder patients: a cohort analysis. u Although all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings u 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. Dr. Richard Kelley Manuscript (2009) Evaluation and Treatment of Patients with Autism and Mitochondrial Disease u Shoffner (2010) Fever plus mitochondrial disease could be risk factors for autistic regression. u Autistic regression occurred in 60.7% (17 of 28), a statistically significant increase over the general autistic spectrum disorder u 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. JAMA article (2010) Journal of American Medical Association December 1, 2010-Vol 304,No. 21 u Mitochondrial dysfunction may influence processes highly dependent on energy, such as neurodevelopment, and contribute to u Autism. In this exploratory study, children with Autism were more likely to have mitochondrial dysfunction, mtDNAoverreplication, and mtDNA deletions than typically developing children.” Frye, Rossignol (2012) Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. u
Mito and Autism- 2012- today Dr. Richard Frye’s research “Most children (79%) who had ASD and mitochondrial disease did not have a u 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) Treatments for biomedical abnormalities associated with autism spectrum u disorder. (2014) Gastrointestinal dysfunction in autism spectrum disorder: the role of the u mitochondria and the enteric microbiome. (2015) Metabolic and mitochondrial disorders associated with epilepsy in children u 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 For many years the “gold standard” of mitochondrial disease diagnosis was a u muscle biopsy. Within the last 5 years, the field has shifted away from muscle biopsy to focus u much more on genetic mutations and genetic testing. Some physicians still do muscle biopsy for confirmation, but the procedure u 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 Dr. Fran Kendall’s article in Autism Science Digest 2011 suggests Tier 1 and u Tier 2 testing: http://www.mitoaction.org/files/AutismOne2011.pdf
Additional Testing Dr. Richard Frye’s paper u Unique acyl-carnitine profiles are potential biomarkers for acquired u mitochondrial disease in autism spectrum disorder. Transl Psychiatry. 2013 Jan 22;3:e220. doi: 10.1038/tp.2012.143.
Genetic Testing Mitochondrial DNA testing (37 genes) u Nuclear DNA testing for mitochondrial genes (1500+genes) u Gene Panels for specific mitochondrial disorders (MELAS, MERF , Leigh’s, etc) u Whole Exome sequencing (30-50% diagnosis rate) u Direct to consumer testing: 23 and me u
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