Mitochondrial Disease Flashcards
what are some brain associated symptoms of Mito diseases?
developmental delays migraines seizures dementia autistic features atypical cerebral palsy neuro-psychiatric disturbances strokes
what are some of the main organ systems affected by Mitochondrial disease?
CNS Muscles Cardiac GI system including Liver Kidneys
what are some effects on Nerves in mito diseases?
absent reflexes fainting neuropathic pain weakness dysautonomia - temperature instability
what are some associated Pancreas issues?
diabetes and exocrine pancreatic failure - inability to make digestive enzymes
parathyroid failure - low calcium
what is different about strokes in pts with Mito disorders?
mitochondria in the smooth muscles cells of the vessels in the brain cause spasms or uncoordinated activities that may lead strokes
difference is that strokes are not due to thrombotic events
what are some muscle issues?
weakness
cramping
hypotonia
muscle pain
what are some common problems in Mitochondrial energy disorders?
central nervous system problems - developmental delays including Austism and Autistic features, loss of function, seizures, hypotonia & weakness
failure to thrive
chronic fatigue
gastrointestinal issues such as chronic constipation
autonomic dysfunction such as irregular heart rate and blood pressure and temperature instability with heat intolerance
mitochondrial genes are inherited exclusively from
mom
what are some methods to test for mitochondrial disease?
functional testing - examining the OXPHOS energy pathway
gene testing - evaluate mtDNA and nuclear mitochondrial genes
biomarker studies - lactate and pyruvate levels, CSF lactate, CPK, urine organic acids, carnitine levels
Radiographic studies - identification of mito related imaging abnormalities
What findings would strongly suggest mitochondrial energy disorders?
brain changes suggestive of Leigh disease or abnormalities in white matter
persistent, significant elevation in lactate (esp. if in the brain) and other specific biochemical features
problems in many body systems
strong family history
what are some GI issues?
pseudo-obstruction dysmotility irritable bowel syndrome gastroesophogeal reflux diarrhea or constipation
Kidney issues?
renal tubular acidosis or wasting
Heart issues?
cardiomyopathy
cardiac conduction defects - heart blocks
Liver issues?
liver failure
hypoglycemia - low blood sugar
Ear or eye issues?
visual loss and blindness ptosis ophthalmoplegia optic atrophy hearing loss and deafness acquired strabismus retintis pigmentosa
what are some systemic issues?
failure to gain weight chronic fatigue unexplained vomiting short stature respiratory problems
Heteroplasmy of mtDNA
explains varying degrees of mito disorders
what is a typical test to diagnosis Mito energy disorders?
muscle tissue biopsy - allows to assess mito structure/size/shape/number
test enzymatic abnormalities of energy producing systems
respirometry studies to measure oxygen comsumption
blue and clear native gels studies to assess protein complexes and supercomplexes to ID defects
How often are ragged red fibers seen?
less than 2.5% of cases
in peds pt, usually normal
most often seen in adult pts with mtDNA gene defects
what does testing of skin fibroblasts and buccal swabs allow?
less invasive biopsy
OXPHOS assays
mtDNA screening screens
37 maternally inherited genes
there are about 1500 genes involved in mitochondrial energy production
what are some metabolic abnormalities that support mitochondrial disease?
increased blood and/or CSF lactate and pyruvate and/or ratio
decreased plasma carnitine
increased blood alanine
generalized aminoaciduria
increase lactate, pyruvate, kreb cycle intermediates, tiglyglycine and 2-oxoadipic acid
treatments are limited but include
CoQ10 L-carnitine Riboflavin Alpha lipoic acid Creatine
what is Autism ?
complex neurobiological disorder
part of group of disorders ASD
associated with rigid routines and repetitive behaviors
cause largely unknown
Do vaccines cause Autism?
NO!!!!
In a UC Davis study, it was found that 60% of ASD pts had …
reduced mitochondrial enzyme function
Complex 1 was affected
Before screening for Mitochondrial disorder, check for …
chromosome abnormalities
inborn errors of metabolism
any other disorders related to the clinical presentations
What are some suggested Tier 1 work ups for ASD patients?
chromosome microarray complete metabolic panel, CBC, CPK ammonia level lactate and pyruvate levels carnitine CoQ10 plasma and urine AA urine organic acids plasma acylcarnitines thyroid function tests
What are some tier 2 tests for ASD patients?
mitochondrial enzyme and/or DNA testing Rett syndrome DNA testing PTEN mutational analysis Gene testing lysosomal enzyme testing peroxisome disease testing CSF studies for lactate and pyruvate, AA and neurotransmitters brain MRI
