Mitochondrial Disorders in Neurology

Mitochondria, computer artwork.
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Mitochondria are fascinating little organelles that dwell in almost every cell in our body. Unlike other parts of the cell, mitochondria are almost a cell of their own. In fact, they are almost entirely separate organisms, with genetic material that is entirely different from the rest of the body. For example, we generally accept that we inherit half of our genetic material from our mother and half from our father.

This is not quite true. Mitochondrial DNA divides in a different fashion and is inherited almost entirely from the mother.

Many scientists believe that mitochondria are an example of a longstanding symbiotic relationship, in which bacteria long ago merged with our cells so that both our cells and the bacteria became dependent on each other. We need mitochondria in order to process most of the energy our cells need to survive. The oxygen we breathe fuels a process that would be impossible without this little organelle.

As intriguing as mitochondria are, they are susceptible to damage just like any other part of our body. Inherited mutations in mitochondrial DNA can lead to a wide array of different symptoms. This can lead to syndromes once thought to be unusual and extremely rare, but are now being seen as more common than previously thought. A group in Northeast England found the prevalence to be about 1 in 15,200 people.

A greater number, about 1 in 200, had a mutation, but the mutations were not symptomatic.

The nervous system relies heavily on oxygen in order to do its job, and that means our nerves need mitochondria to function well. When mitochondria go wrong, the nervous system is often the first to suffer.

Symptoms of Mitochondrial Disease

The most common symptom caused by mitochondrial disease is a myopathy, meaning a disease of muscle.

Other potential symptoms include vision problems, thinking problems, or a combination of symptoms. Symptoms often cluster together to form one of several different syndromes.

  • Chronic Progressive External Ophthalmoplegia (CPEO)- in CPEO, the eye muscles slowly become paralyzed. This usually occurs when people are in their thirties, but can occur at any age. Double vision is relatively rare, but other visual problems may be discovered by a doctor's examination. Some forms, especially when found in families, are accompanied by hearing problems, speech or swallowing difficulties, neuropathies, or depression.

  • Kearns-Sayre syndrome- Kearns-Sayre syndrome is almost he same as CPEO, but with some extra problems and an earlier age of onset. Problems usually begin when people are under the age of 20. Other problems include pigmentary retinopathy, cerebellar ataxia, cardiac problems and intellectual deficits. Kearns-Sayre syndrome is more aggressive than CPEO, and can lead to death by the fourth decade of life.

  • Leber Hereditary Optic Neuropathy (LHON)- LHON is an inherited form of vision loss which causes blindness in young men.

  • Leigh Syndrome-- Also known as subacute necrotizing encephalomyelopathy, Leigh syndrome usually occurs in very young children. the disorder causes ataxia, seizures, weakness, developmental delays, dystonia, and more. Magnetic resonance imaging (MRI) of the brain shows abnormal signal in the basal ganglia. The disease is usually fatal within months.

  • Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS)- MELAS is one of the most common types of mitochondrial disorders. It is inherited from the mother. The disease causes episodes similar to strokes, which can cause weakness or vision loss. Other symptoms include seizures, migraine, vomiting, hearing loss, muscle weakness, and a short stature. The disorder usually begins in childhood and progresses to dementia. It can be diagnosed by elevated levels of lactic acid in the blood as well as typical "ragged red fiber" appearance of muscle under a microscope.

  • Myoclonic epilepsy with ragged red fibers (MERRF)- Myoclonus is a very fast muscle jerk, similar to what many have just before we fall asleep. The myoclonus in MERRF is more frequent and is followed by seizures, ataxia, and muscle weakness. Deafness, vision problems, peripheral neuropathy, and dementia may also occur.

  • Maternally inherited deafness and diabetes (MIDD)- This mitochondrial disorder usually affects people between 30 to 40 years of age. In addition to hearing loss and diabetes, people with MIDD can have vision loss, muscle weakness, cardiac problems, kidney disease, gastrointestinal disease, and short stature.

  • Mitochondrial neurogastrointestinal encephalopathy (MNGIE)- This causes severe immobility of the intestines, which can lead to abdominal distress and constipation. Problems with eye movement are also common, as are neuropathies and white matter changes in the brain. The disorder comes on anywhere from childhood to the fifties but is most common in children.

  • Neuropathy, ataxia and retinitis pigmentosa (NARP)- In addition to peripheral nerve problems and clumsiness, NARP can cause developmental delay, epilepsy, weakness, and dementia.

Other mitochondrial disorders include Pearson syndrome (sideroblastic anemia and pancreatic dysfunction), Barth syndrome (X-linked cardiomyopathy, mitochondrial myopathy, and cyclic neutropenia), and growth retardation, amino aciduria, cholestasis, iron overload, lactic acidosis, and early death (GRACILE).

Diagnosing Mitochondrial Diseases

Because mitochondrial disease can cause a bewildering range of symptoms, these disorders can be hard even for trained physicians to recognize. In the unusual situation where all symptoms seem classic for a particular disorder, genetic testing can be done to confirm the diagnosis. Otherwise, other tests may be necessary.

Mitochondria are responsible for aerobic metabolism, which most of us use day to day in order to move. When aerobic metabolism is exhausted, as in intense exercise, the body has a backup system that results in the build-up of lactic acid. This is the substance that makes our muscles ache and burn when we strain them for too long. Because people with mitochondrial disease have less ability to use their aerobic metabolism, lactic acid builds up, and this can be measured and used as a sign that something is wrong with the mitochondria. Other things can increase lactate too, however. For example, lactic acid in cerebrospinal fluid may be elevated after seizures or stroke. Furthermore, some types of mitochondrial disease, like Leigh syndrome, frequently have lactate levels that are within normal limits.

A basic evaluation can include lactate levels in plasma and cerebrospinal fluid. Electrocardiograms can evaluate for arrhythmias, which can be fatal. A magnetic resonance image (MRI) can look for white matter changes. Electromyography can be used to investigate for muscle disease. If there is concern for seizures, electroencephalography can be ordered. Depending on symptoms, audiology or ophthalmology testing may also be recommended.

Muscle biopsy is one of the most reliable ways of diagnosing mitochondrial disorders. Most mitochondrial diseases come with a myopathy, sometimes even if there are no obvious symptoms like muscle soreness or weakness.

Treatment in Mitochondrial Diseases

At this time, there is no guaranteed treatment for mitochondrial disorders. The focus is on managing symptoms as they arise. However, a good diagnosis can help prepare for future developments, and in the case of an inherited illness, may impact family planning.


In short, a mitochondrial disease should be suspected when there is a combination of symptoms involving muscle heart, brain, or eyes. While maternal inheritance is also suggestive, it is possible and even common for mitochondrial disease to result from mutations in nuclear DNA, due to interactions between the genetic material of the nucleus and the mitochondria. Furthermore, some diseases are sporadic, meaning they happen for the first time without being inherited at all. Mitochondrial diseases are still relatively rare and are best managed by a specialist with a solid understanding of this class of neurological disease.


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