Mitochondrial disease

Mitochondrial diseases are a group of disorders relating to the mitochondria, the organellesthat are the "powerhouses" of the eukaryotic cellsthat comprise higher-order lifeforms (including humans). The mitochondria convert the energy of food molecules into the ATPthat powers most cell functions.

Mitochondrial diseases comprise those disorders that in one way or another affect the function of the mitochondria and/or are due to mitochondrial DNA. Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because that mitochondria are so critical to cell function. The subclass of these diseases that have neuromuscular disease symptoms are often referred to as a mitochondrial myopathy.

Mitochondrial inheritance

Mitochondrial inheritance behaves differently from the sort of inheritance that we are most familiar with. Regular nuclear DNAhas two copies per cell (except for sperm and egg cells). One copy is inherited from the father and the other from the mother. Mitochondria, however, contain their own DNA, and contain typically from five to ten copies, all inherited from the mother (for more detailed inheritance patterns, see mitochondrial genetics). When mitochondria divide, the copies of DNA present are divided randomly between the two new mitochondria, and then those new mitochondria make more copies. As a result, if only a few of the DNA copies inherited from the mother are defective, mitochondrial division may cause most of the defective copies to end up in just one of the new mitochondria. Once more than half of the DNA copies are defective, mitochondrial disease begins to become apparent, this phenomenon is called 'threshold expression'.

It should be noted, however, that not all of the enzymes and other components necessary for proper mitochondrial function are encoded in the mitochondrial DNA. Most mitochondrial function is controlled by nuclear DNA instead.

To make things even more confusing, mutations to mitochondrial DNA occur frequently, due to the lack of the error checking capability that nuclear DNA has. This means that a mitochondrial disorder can occur spontaneously rather than be inherited. Further, sometimes the enzymes that control mitochondrial DNA duplication (and which are encoded for by genes in the nuclear DNA) are defective, causing mitochondrial DNA mutations to occur at a rapid rate.

Defects and symptoms

The effects of mitochondrial disease can be quite varied. Since the distribution of defective DNA may vary from organ to organ within the body, the mutation that in one person may cause liver disease might in another person cause a brain disorder. In addition, the severity of the defect may be great or small. Some minor defects cause only "exercise intolerance", with no serious illness or disability. Other defects can more severely affect the operation of the mitochondria and can cause severe body-wide impacts. As a general rule, mitochondrial diseases are worst when the defective mitochondria are present in the musclesor nerves, because these are the most energy-hungry cells of the body.

However, even though mitochondrial disease varies greatly in presentation from person to person, several major categories of the disease have been defined, based on the most common symptoms and the particular mutations that tend to cause them:

• OMIM157640Progressive external ophthalmoplegia(PEO)
  • progessive ophthalmoparesisis the cardinal feature
  • symptomatic overlap with many of the illnesses described below
• OMIM520000Diabetes and deafness(DAD)
  • this combination at an early age can be due to mitochondrial disease
  • Diabetes mellitusand deafnesscan be found together for other reasons as well
• OMIM535000Leber hereditary optic neuropathy(LHON)
  • visual loss beginning in young adulthood
  • Wolff-Parkinson-White syndrome
  • multiple sclerosis-type disease
• OMIM540000Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS)
  • varying degrees of cognitive impairment and dementia
  • lactic acidosis
  • strokes
  • transient ischemic attacks
  • hearing loss
  • dysmotility
  • weight loss
• OMIM545000Myoclonic epilepsy and ragged-red fibers(MERRF)
  • progressive myoclonic epilepsy
  • clumps of diseased mitochondria accumulate in the subsarcolemmal region of the muscle fiber and appear as "ragged-red fibers" when muscle is stained with modified Gomori trichrome stain
  • short stature
• OMIM256000Leigh syndrome, subacute sclerosing encephalopathy
  • after normal development the disease usually begins late in the first year of life, but the onset may occur in adulthood
  • a rapid decline in function occurs and is marked by seizures, altered states of consciousness, dementia, ventilatory failure
• OMIM551500Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
  • progressive symptoms as described in the acronym
  • dementia
• OMIM530000Kearn-Sayre syndrome(KSS)
  • external ophthalmoplegia
  • cardiac conduction defects
  • sensory-neural hearing loss
• OMIM603041Myoneurogenic gastrointestinal encephalopathy(MNGIE)
  • gastrointestinal pseudo-obstruction
  • neuropathy
• OMIM238800Luft disease

External links

• Mitochondrial Disease Action Committee
• United Mitochondrial Disease Foundation
• Muscular Dystrophy Association Mito Information

This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/Mitochondrial+disease Wikipedia article Mitochondrial disease.