Mito

Question 1

What is your basal metabolic rate?

Answer 1

minimum # of calories needed at rest for energy for overall cell/organ function

Question 2

What tissues require the most of our BMR?

Answer 2

Organs (brain, liver, heart, kidneys) - 58%

Skeletal muscle (22%)

Question 3

Why are vitamine necessary?

Answer 3

function as cofactors that are necessary for pathways

Question 4

If your pH drops below 7.2 you are in:

Answer 4

acidosis

Question 5

If your pH rises above 7.5 you are in:

Answer 5

alkalosis

Question 6

What macromolecule are neurotransmitters made from?

Answer 6

amino acids

Question 7

What level should our blood glucose be at for adequate organ fxn?

Answer 7

80-120mg/dl

Question 8

Fatty acids are the main source of energy for what organs?

Answer 8

muscle and heart

Question 9

What’s the most effective way to measure enzyme activity?

Answer 9

tissue biopsy

Question 10

Mitochondrial conditions result from mutations in what genes?

Answer 10

mtDNA or nDNA

Question 11

Defects in the Krebs cycle are often caused by? Fatty acids? respiratory chain?

Answer 11

AR nDNA
nDNA
mtDNA from mom and AR conditions

Question 12

What are some other functions of mitochondria?

Answer 12

DNA synthesis
Heme synthesis
Urea cycle
hormone synthesis
neurotransmitter metabolism
free radical production and detox

Question 13

What happens in cells with defective mitochondria?

Answer 13

• no ATP
• severe impact of other mito fxn
• free radicals accumulate
• lactic acidosis

Question 14

How many oxidative phosphorylation complexes exist? What genes code for them? How can we measure their activity?

Answer 14

5
mtDNA and nDNA
fresh or frozen muscle biopsy

Question 15

How many nDNA genes do we have? mtDNA?

Answer 15

850 nDNA vs. 13 mtDNA

Question 16

How do nDNA mutations result in disease (this came from our lecture but I don’t like it now that I see it again)?

Answer 16

autosomal recessive inheritance

Question 17

What is unique about mtDNA?

Answer 17

• closed, circular DNA
• maternally inherited
• thousands of copies per cell
• copy number is dynamic

Question 18

3243A>G in mtDNA accounts for 90% of what condition?

Answer 18

MELAS

Question 19

What are three factors we should consider with mito conditions?

Answer 19

heteroplasmy
tissue distribution
threshold effect (vulnerability of each tissue to impaired oxidative metabolism)

Question 20

how common are mitochondrial diseases?

Answer 20

1:4,000 in children in US by age 10

Question 21

Mitochondrial diseases are typically _______ and _________.

Answer 21

progressive and mutlisystemic

Question 22

What types of organs are most impacted by mito conditions? ex?

Answer 22

those with high energy demand

skeletal and cardiac muscle, endocrine organs, kidney, motility in intestinal tract, retina, central nervous system

Question 23

when might we suspect a mito condition?

Answer 23

seeing involvement of 3 or more organ systems without a unifying dx

Question 24

What are some of the neurologic red flags for mito conditions?

Answer 24

• stroke-like lesions in non-vascular patterns
• basal ganglia disease
• encephalopathy
• intractable epilepsy
• myoclonus (esp. in children)
• ataxia
• MRI findings consistent with Leigh
• MRS peaks

Question 25

What are some of the cardio red flags for mito conditions?

Answer 25

- hypertrophic cardiomyopathy with rhythm disturbance - unexplained heart block in child - cardiomyopathy with lactic acidosis - dilated cardiomyopathy with muscle weakness - Wolff-Parkinson-White arrhythmia

Question 26

What are some of the ophthalmologic red flags for mito conditions?

Answer 26

-retinal degenration with signs of night blindness, color-vision deficits, decreased visual acuity, or pigmentary retinopathy -not able to move eyes -roving eyes -ptosis (droopy eyelids) sudden blindness

Question 27

What are some of the GI red flags for mito conditions?

Answer 27

- unexplained or valproate liver-failure - severe dysmotility - pseudo-obstructive episodes

Question 28

What are some other red flags for mito conditions?

Answer 28

- newborn, infant, or young child wit unexplained hypotonia, weakness, FTT, and metabolic acidosis (particularly lactic) - exercise intolerance not proportionate to weakness - hypersensitivity to general anesthesia - episodes of acute rhabdomyolysis - fibromyalgia in young people

Question 29

What are the most common expression of enchephalomyopathy in mito conditions?

Answer 29

hearing impairment, migraine-like headaches, and seizures

Question 30

does a normal lactate rule out mitochondrial disorders?

Answer 30

no - lactate may only rise during episodes Leigh, Kearns-Sayre syndrome, Leber, and others frequently occur with little or no lactate elevation

Question 31

What deos MELAS stand for? When does MELAS typically present? Features? Main mutation?

Answer 31

MItochondrial Encephalopathy-Lactic Acidsosis-Stroke-Like episodes - childhood to early adulthood - recurrent strokes that manifest as migraine-like headaches, vomiting and (less often) seizures, and can cause permanent brain damage - can occur in infancy with DD and LD before first stroke mutation: m.3243A>G (>80%)

Question 32

How can we treat MELAS?

Answer 32

Arginine may have some protective benefit

Question 33

When does KSS present? Its features?

Answer 33

- <20y - progressive external ophthalmoplegia (initail) and pigmentary retinopathy, salt-and-pepper pigmentation in retina, conduction block in heart, ataxia

Question 34

What mutation(s) often cause KSS?

Answer 34

deletions of mtDNA common one is m.8470_13446del4977

Question 35

When does Pearson syndrome present? Features? If these individuals survive they often develop:

Answer 35

infancy severe anemia and malfunction of pancreas KSS

Question 36

When doe Leigh syndrome present? Features? Leads to?

Answer 36

infancy brain abn that may result in ataxia, seizures, impaired vision and hearing, DD and altered control over breathing causes muscle weakness (swallowing, speech, and eye movement) poor outcome

Question 37

This condition presents in infancy with muscle weakness and/or liver failure and possibly brain abn.

Answer 37

MDS

Question 38

This condition presents in late childhood to adolescence with myoclonus, seizures, ataxia and muscle weakness. It also can cause hearing impairment and short stature.

Answer 38

MERRF (myoclonus epilepsy with ragged red fibers)

Question 39

This condition presents typically <20y with PEO, ptosis, limb weakness and GI problems (dhronic diarrhea and abdominal pain) and peripheral neuorpathy.

Answer 39

MNGIE

Question 40

This condition presents in infancy to adulthood with neuropathy, ataxia, and retinitis pigmentosa. Perhaps DD, seizures, and dementia

Answer 40

NARP