Mito Flashcards
At _____ % heteroplasmy, the cell exceeds the threshold for normal functioning and is said to be dysfunctional
70%
Which organs are most likely to be affected by metabolic conditions
Organs that consume large amounts of energy such as the brain and liver
What would you recommend for a patient diagnosed with MERRF
Eat small frequent meals high in carbohydrates
For what patient report would you be least concerned for risk of mitochondrial disorders
Single organ affected
Metabolism
how the body functions by generating energy through intricate chemical steps from daily nutrients and food consumption
Basal metabolic rate
resting rate expenditure - minimum calories needed at rest for energy for overall cell/organ function
Systems that use most metabolism
organs - brain, liver, heart and kidneys
Normal pH
7.4
of amino acids
20
Proteins are made of
amino acids
Catabolism
Protein breakdown
Blood glucose level
80-120 mg/dl
Extra glucose is stored as
glycogen
what is the main energy source for cells
glucose
fatty acids are absorbed through the ____ and processed in the _____
gut and liver
What are the main source of energy for muscle and heart
fatty acids
Energy metabolism occurs in the
mitochondria
Need what kind of sample to measure enzyme activity
biopsy of tissue
Organs that have high energy demand
skeletal, cardiac, endocrine, kidney, intestinal tract, retina, CNS
Mitochondrial disease
chronic disorders that occur when mitochondria in numerous cells fail to produce sufficient energy for adequate function with subsequent organ failure
Other functions of mitochondria
Purine/pyrimidine biosynthesis
Heme synthesis
Urea cycle
Cholesterol metabolism/hormone synthesis
Neurotransmitter metabolism
free radical production and detoxification
What happens in cell with defective mitochondria
no ATP
severe impact on other mitochondrial functions
backlog of unused fuel molecules and oxygen
inadequate oxygen supply
lactic acidosis damages muscle and nerve tissue
reactive oxygen species
How to measure activity of oxidative phophorylation (respiratory chain)
fresh or frozen muscle biopsy
How many genes does it take to make a mitochondria
3000
Electron transport chain is controlled by both
mtDNA and nDNA
nDNA - 850 genes
mtDNA - 13 genes
nDNA for electron transport chain is
AR
mtDNa is
maternal
Circular
Only how many genes are designated for making ATP
100 out of 3000
Heteroplasmy
presence of a mixture of mutant and normal mtDNA
Threshold effect
vulnerability of each tissue to impaired oxidative metabolism
Mitochondrial disease incidence
1:4000 by age 10
mitochondrial encephalomyopathy
mito problems in muscular and neurological
Neurologic red flags for mitochondrial disease
MELAS
Basal ganglia disease (Leigh Syndrome)
Encephalopathy
Neurodegeneration
Epilepsia partialis continua
Myoclonus -MERFF
Ataxia - NARP
MRI findings consistent with Leigh disease
Characteristic MRS peaks
Cardio red flags for mitochondrial disease
Hypertrophic cardiomyopathy with rhythm disturbance
unexplained heart block in child
cardiomyopathy with lactic acidosis
dilated cardiomyopathy with muscle weakness
Wolff-Parkinson-White arrhythmia
Ophthalmologic red flags for mitochondrial disease
retinal degeneration
Ophthalmoplegia/paresis (not able to move eyes)
Fluctuating, dysconjugate eye movements (roving eyes)
Ptosis (droopy eyelids)
Sudden- or insidious-onset optic neuropathy/atrophy (sudden blindness)
Gastroenterologic red flags for mitochondrial disease
unexplained or valproate-induced liver failure
severe dysmotility
pseudo-obstructive episodes
Other red flags for mitochondrial disease
newborn with hypotonia, weakness, FTT, and metabolic acidosis (specificially lactic acidosis)
Exercise intolerance
Hypersensitivity to general anesthesia
Episodes of acute rhabdomyolysis
Myopathy
muscle weakness and wasting, and exercise intolerance
Weakness and wasting in face and neck muscles
-slurred speech
-difficulty swallowing
Encephalomyopathy features
hearing impairment, migraine-like headaches and seizures
headaches and seizures accompanied by stroke
Diagnostic evaluation of mitochondrial disease
lactic acidosis (not sensitive or specific)
Pathogenic mtDNA or nDNA mutation
MELAS (mitochondrial encephalopathy-lactic acidosis-stroke-like episodes) features
recurrent strokes in the brain
-manifest as migraine-like headaches, vomiting, and seizures
Seizures - tonic-clonic or myoclonic
PEO
General muscle weakness
Exercise intolerance
hearing loss
diabetes
short stature
pancreatitis, ischemic colitis, and intestinal obstruction
numbness, tingling sensation, and pain in extremities
psychiatric disorders
Autism
Hypo or hyperthyroidism
Ataxic gate
kidney damage
MELAS (mitochondrial encephalopathy-lactic acidosis-stroke-like episodes) onset
childhood to early adulthood
MELAS (mitochondrial encephalopathy-lactic acidosis-stroke-like episodes) gene
m.3243A<G (80%)
MELAS (mitochondrial encephalopathy-lactic acidosis-stroke-like episodes) treatment
Arginine
Vasodilation
KSS (Kearns-Sayre Syndrome) onset
before age 20
KSS (Kearns-Sayre Syndrome) features
progressive external opthalmoplegia (PEO)
Pigmentary retinopathy
salt-and-pepper pigmentation in retina
Conduction block in heart
Ataxia
Possible ID, delayed sexual maturation, and SS
KSS (Kearns-Sayre Syndrome) genetics
deletion in mtDNA in 90%
common deletion is m.8470_1344del4977
usually deletions are present in all tissues
Pearson Syndrome onset
infancy
Pearson syndrome features
severe anemia
malfunction of the pancreas
those who survive go on to develop KSS
Leigh Syndrome onset
infancy
Leigh Syndrome features
brain abnormalities
-result in ataxia, seizures, impaired vision and hearing, DD, and altered control over breathing
muscle weakness
-prominent effects on swallowing, speech, and eye movements
Respiratory failure
Leigh Syndrome genetics
SURF-1
MDS (Mitochondrial DNA Depletion Syndrome) onset
infancy
MDS (Mitochondrial DNA Depletion Syndrome) features
muscle weakness
liver failure
brain abnormalities
floppiness
feeding difficulties
DD
PEO
Seizures
MERFF (Myoclonus Epilepsy with Ragged Red Fibers) onset
late childhood to adolescence
MERFF (Myoclonus Epilepsy with Ragged Red Fibers) features
myoclonus (muscle spasms)
seizures
ataxia
muscle weakness
hearing impairment
SS
MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) onset
before age 20
MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) features
PEO
Ptosis
Limb weakness
gastrointestinal problems
-chronic diarrhea and abdominal pain
Peripheral neuropathy
NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) onset
infancy to adulthood
NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) features
neuropathy
Ataxia
Retinitis pigmentosa
DD
Seizures
Dementia
Cofactors examples
Nicotinamide
Thiamine
Riboflavin
Coenzyme Q10
Coenzyme Q10
shuttles electrons from Complex I and II to Complex III
Carnitine
Shuttles fatty acids into mitochondria for oxidation
