Term
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Definition
The “powerhouse” of the cell. Creates ATP from glucose. There are 3,000 to 5,000 per cell.
Well characterized genome. Brain, heart, and skeletal muscles most affected by mitochondrial abnormalities.
Look like bacteria because derived from bacteria.
Have circular chromosome (2-10 copies) and have their own rRNA, tRNA, and mRNA to encode respiratory chain subunits. Randomly segregate to daughter cells in cell division. |
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Term
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Definition
Some cells may have more mitochondria than others, and some mitochondria might have the mutation while others don’t.
You might have more than one mitochondrial genome in different proportions.
Because of heteroplasmy, mitochondrial diseases can have different severities in different individuals. |
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Term
| The mitochondrial genome (facts) |
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Definition
1. Well characterized
2. Circular (2-10 per mitochondria)
3. Does not have introns
4. The mutation rate is 10x the mutation rate of that of nDNA
5. Inherited through the mother’s ovum |
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Term
| Leber Hereditary Optic Neuropathy (LHON) |
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Definition
A mitochondrial disorder caused by a missense mutation in the protein coding mitochondrial DNA.
Clinical features include the rapid loss of central vision due to optic nerve death. This is usually the only symptom.
Heteroplasmy is usually minimal and expression is uniform in families. |
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Term
| Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like Episodes (MELAS) |
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Definition
A mitochondrial disease.
Clinical features include weakness of the muscles throughout the body (mitochondrial myopathy), encephalopathy (disease of the central nervous system), lactic acidosis, and stroke.
Mitochondrial myopathy
Enchephalopathy
Lactic acidosis
Stroke |
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Term
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Definition
A mitochondrial disease caused by multiple mutations -- almost a general catch all.
Symptoms usually appear by 2 years of age. Often comes and goes but gets progressively worse. Very variable. It’s clinical features include congenital lactic acidosis and spongiform degeneration of the brain. |
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Term
| Myoclonic Epilepsy with Ragged Red Fiber Syndrome (MERRF) |
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Definition
A mitochondrial disease.
The classic symptoms include
- myoclonus (brief, sudden, twitching muscle spasms)
- epileptic seizures
- ataxia (impaired coordination)
- ragged-red fibers.
Additional symptoms include hearing loss, lactic acidosis, short stature, exercise intolerance, dementia, cardiac defects, eye abnormalities, and speech impediments.
Most are inherited from the mother. Heteroplasmy does apply -- not all individuals will show symptoms. |
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Term
| Kearns-Sayre Syndrome (KSS) |
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Definition
A mitochondrial disease.
Clinical features include drooping eyelids (ptosis). Other eye muscles eventually become involved resulting in the paralysis of eye movement. Degeneration of the retina usually causes difficulty seeing in dimly lit environments. |
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Term
| Are all mitochondrial disorders caused by a change in the mitochondrial genome? |
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Definition
| No -- a mitochondrial disorder can be caused by a change in the mitochondrial genome or the nuclear DNA. |
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Term
| When should you suspect a mitochondrial disorder? |
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Definition
1. Early onset disease with rapid progression
2. Delayed onset with progression
3. Fluctuating course (especially after illness)
4. Multisystem diseases affecting multiple organs
5. Neurological features like dementia or seizures
6. Myopathy
7. Hearing loss
8. Diabetes |
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Term
| Why can there be delayed onset of a mitochondrial disease? |
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Definition
1. Aging causes a decline in the mitochondria anyway
2. There is a high spontaneous mutation rate of mitochondrial DNA
3. Mito DNA can be damaged by free radicals
4. Stressful events like infection can push a body "over the edge" |
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Term
| What are some classic lab findings for a mitochondrial disorder? |
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Definition
1. Lactic acidosis
2. Ragged red fibers in a muscle biopsy
3. Myopathic potentials in an electrography
4. An abnormal nerve conduction study
5. Hearing loss
6. Cardiac conduction defects
7. Abnormal head MRI
8. Defective oxidative phosphoryation in a biochemical study
9. A genetic test for a mito DNA mutation |
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Term
| How does mitochondrial disease lead to hearing loss? |
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Definition
- Mitochondrial mutation causes sensitivity to aminoglycosides, an antibiotic given to newborns for infections
- After one dose of this, years later someone will lose their high frequency hearing
- Mean age of onset is 20 after hair cells have degenerated |
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Term
| What are some treatments for mitochondrial conditions? |
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Definition
1. Antioxidants
2. Supplemental carnitine
3. Riboflavin (used in energy pathways)
4. Vitamins and minerals
5. Medication to shut down bad mitochondria is being tested
6. Avoid oxidants like cigarrettes |
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