Flashcards in Mitochondrial Disease Deck (29)
what are some of the main organ systems affected by Mitochondrial disease?
GI system including Liver
what are some brain associated symptoms of Mito diseases?
atypical cerebral palsy
what are some effects on Nerves in mito diseases?
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?
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
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
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?
irritable bowel syndrome
diarrhea or constipation
renal tubular acidosis or wasting
cardiac conduction defects - heart blocks
hypoglycemia - low blood sugar
Ear or eye issues?
visual loss and blindness
hearing loss and deafness
what are some systemic issues?
failure to gain weight
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
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
increase lactate, pyruvate, kreb cycle intermediates, tiglyglycine and 2-oxoadipic acid
treatments are limited but include
Alpha lipoic acid
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?
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 ...
inborn errors of metabolism
any other disorders related to the clinical presentations
What are some suggested Tier 1 work ups for ASD patients?
complete metabolic panel, CBC, CPK
lactate and pyruvate levels
plasma and urine AA
urine organic acids
thyroid function tests