Flashcards in Mitochondrial Disease Deck (29)
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what are some of the main organ systems affected by Mitochondrial disease?
CNS
Muscles
Cardiac
GI system including Liver
Kidneys
1
what are some brain associated symptoms of Mito diseases?
developmental delays
migraines
seizures
dementia
autistic features
atypical cerebral palsy
neuro-psychiatric disturbances
strokes
2
what are some effects on Nerves in mito diseases?
absent reflexes
fainting
neuropathic pain
weakness
dysautonomia - temperature instability
3
what are some associated Pancreas issues?
diabetes and exocrine pancreatic failure - inability to make digestive enzymes
parathyroid failure - low calcium
4
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
5
what are some muscle issues?
weakness
cramping
hypotonia
muscle pain
6
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
7
mitochondrial genes are inherited exclusively from
mom
8
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
9
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
10
what are some GI issues?
pseudo-obstruction
dysmotility
irritable bowel syndrome
gastroesophogeal reflux
diarrhea or constipation
11
Kidney issues?
renal tubular acidosis or wasting
12
Heart issues?
cardiomyopathy
cardiac conduction defects - heart blocks
13
Liver issues?
liver failure
hypoglycemia - low blood sugar
14
Ear or eye issues?
visual loss and blindness
ptosis
ophthalmoplegia
optic atrophy
hearing loss and deafness
acquired strabismus
retintis pigmentosa
15
what are some systemic issues?
failure to gain weight
chronic fatigue
unexplained vomiting
short stature
respiratory problems
16
Heteroplasmy of mtDNA
explains varying degrees of mito disorders
17
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
18
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
19
what does testing of skin fibroblasts and buccal swabs allow?
less invasive biopsy
OXPHOS assays
20
mtDNA screening screens
37 maternally inherited genes
there are about 1500 genes involved in mitochondrial energy production
21
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
22
treatments are limited but include
CoQ10
L-carnitine
Riboflavin
Alpha lipoic acid
Creatine
23
what is Autism ?
complex neurobiological disorder
part of group of disorders ASD
associated with rigid routines and repetitive behaviors
cause largely unknown
24
Do vaccines cause Autism?
NO!!!!
25
In a UC Davis study, it was found that 60% of ASD pts had ...
reduced mitochondrial enzyme function
Complex 1 was affected
26
Before screening for Mitochondrial disorder, check for ...
chromosome abnormalities
inborn errors of metabolism
any other disorders related to the clinical presentations
27
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
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