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Mitochondrial Myopathies
Fact Sheet #16
1. Are Mitochondrial Myopathies also known by other names?
Yes, the mitochondrial myopathies are sometimes referred to as mitochondrial disorders of energy metabolism, or MITEM disorders. Since these disorders affect the oxidative phosphorylation pathway, they are also sometimes referred to as OXPHOS disorders. Some of the specific names of this group of disorders are:
| MELAS: |
Myoclonic epilepsy, lactic acidosis and stroke-like episodes |
| MERRF: |
Mitochondrial encephalopathy and ragged red fibres. |
| KSS: |
Kearns-Sayre Syndrome (or Oculocraniosomatic neuromuscular disorder) |
| LHON: |
Lebers Hereditary Optic Neuropathy |
| LS: |
Leigh Syndrome |
| PS: |
Pearson Syndrome |
2. What are Mitochondrial Myopathies?
The term mitochondrial myopathy describes a highly variable group of disorders that share the common feature of reduced energy production in the body’s tissues, particularly muscles. All tissues are composed of small units called cells. Each cell contains a nucleus, and many smaller structures known as mitochondria. The mitochondria process the breakdown products of food and the oxygen that we breathe to produce energy required by the cell. In mitochondrial myopathies, the biochemical processes in the mitochondria are abnormal and energy production is reduced. Muscle tends to be particularly affected as it requires a lot of energy, but other tissues such as the brain, eyes and heart muscle may also be involved. Under the microscope, the mitochondria in muscle from affected individuals look abnormal, and they often accumulate around the edges of muscle fibres. This gives a particular pattern upon staining with a particular dye, known as ‘ragged-red’ fibres, and this is usually how mitochondrial myopathies are diagnosed. Mitochondria use a shuttle system of enzymes in what is called the respiratory chain to produce energy, from food and oxygen. When mitochondria from individuals affected with mitochondrial myopathies are studied biochemically, a block in this shuttle system can usually be demonstrated.
3. What causes Mitochondrial Myopathies?
Mitochondrial myopathies can be inherited, or can arise spontaneously in the mitochondrial genome. Due to the second scenario, some individuals with mitochondrial myopathies do not always have similarly affected relatives. Recent research has provided a lot of information about the genetic aspects of mitochondrial myopathies. There are two sources of DNA in the cell. Our 46 chromosomes are housed in the nucleus and the mitochondrial DNA (mtDNA) is located in the mitochondria. Nuclear genes are inherited from both parents. However, mitochondrial genes are inherited exclusively from the mother.
We know that in about some of the individuals affected with mitochondrial myopathies a substantial section of the mitochondrial DNA are missing (deleted). Most of these individuals do not have affected relatives and it seems likely that the deletions arise either during egg cell production in their mothers, or very early in development of the embryo. Deletions are particularly common in individuals with eye muscle weakness and the Kearns-Sayre syndrome. Approximately one third of mitochondrial myopathies are caused by more subtle changes in mitochondrial genes, called point mutations. These most commonly occur in individuals with symptoms such as involuntary jerks, fits, unsteadiness, stroke like episodes or deafness, with or without muscle weakness (MERRF, MELAS, Leigh syndrome, LHON). Only about one half of people with point mutations have affected relatives, and the genetic mutation can be detected in their maternal relatives. Point mutations can be detected in blood samples in the majority of affected individuals, but deletions can only be detected in muscle samples. In some mitochondrial disorders genes that are located in the nucleus (not in the mtDNA) are responsible for the disorder.
4. What are the symptoms and which muscles are affected?
Mitochondrial Myopathies affect individuals in many ways. The most common problem is a combination of mild muscle weakness in the arms and legs together with droopy eyelids and difficulty in moving the eyes. The latter is known as chronic progressive external opthalmoplegia (CPEO). Other people do not have problems with their eye muscles, but have weakness of the arms and legs which gets worse after exertion. This may be associated with nausea and headache. Sometimes muscle weakness is obvious in small babies if the illness is severe, and they may have difficulties in feeding and swallowing.
Although it is much less common, Mitochondrial Myopathies can affect the brain in either children or adults. This can give rise to unsteadiness, fits, involuntary movements, and episodes resembling strokes. If they occur, these features are nearly always apparent early on in the course of the illness and are unlikely to develop later in mildly affected people. The light-sensitive membrane at the back of the eye (the retina) is often seen to be affected (abnormal accumulation of pigment, retinitis pigmentosa) when looked at through an opthalmoscope, although this does not usually give rise to visual loss. Deafness may also occur. Other parts of the body may be involved, such as the electrical conduction of the heart. A particular combination of features which occur in mitochondrial myopathies are sometimes referred to as the Kearns-Sayre syndrome; this combination of eye muscle weakness, unsteadiness, involvement of the retina, and problems with the cardiac conduction system which may require the insertion of a pacemaker.
5. How are Mitochondrial Myopathies inherited?
Genetic counselling in mitochondrial myopathies is quite complex, and advice depends on the type of symptoms that are observed, the presence or absence of a family history, and the results of genetic studies of blood and muscle samples. The vast majority of mitochondrial myopathies follow a maternal inheritance pattern. The risk of having affected children or brothers and sisters has to be assessed on an individual basis. As these are genetic conditions, genetic counselling is strongly recommended. Genetic counselling provides information on the inheritance pattern, risks to other family members, prognosis, psycho-social support, as well as information about diagnostic testing, carrier testing, preclinical and prenatal testing (where available).
6. How are Mitochondrial Myopathies diagnosed?
It is a complex procedure to diagnose mitochondrial myopathies. The clinical pictures of the different affected individuals can be diverse. To establish a proper diagnosis it is important to get a complete history of the affected individual and his/her family. A clinical examination will follow with several blood tests that will be used to look for certain metabolites like lactate. Tests will be done according to the systems involved, as we know that in some of the mitochondrial myopathies multi-system organ involvement is present. In some instances a muscle biopsy or enzyme analysis on muscle might be indicated. DNA studies on blood and muscle can also be performed to identify mutations within the mitochondrial genes.
7. Is there a cure?
Unfortunately, there is no cure at present for the mitochondrial disorders.
8. Is there any treatment?
No single drug, diet or vitamin has emerged as a 'miracle' cure for mitochondrial myopathies. It is also important to know that two different affected individuals with the same mutations may respond completely differently to the same treatment, therefore no individual should receive a specific drug just because he/she has a specific mitochondrial mutation. In some disorders L-carnitine has been useful. Other drugs that are sometimes used are: coenzyme Q10, vitamin E, vitamin B-complex and biotin. It is essential that you consult with your doctor on any medication, since these drugs are not effective in all individuals affected with Mitochondrial Myopathies.
9. Is there a risk during anaesthesia?
Mitochondrial myopathies are one of the disorders that appear unlikely to be associated with malignant hyperthermia. However, it is always recommended that the presence of a disorder affecting muscle be mentioned to your doctor.
10. Has research been conducted on Mitochondrial Myopathies in South Africa?
Research programmes are conducted in the departments of Human Genetics and Paediatrics at the University of Pretoria, the department of Human Genetics at SAIMR and the department of Chemical Pathology at UCT. Some of these centres offer a mitochondrial DNA diagnostic service as well as clinical assessment of affected individuals. The department of Biochemistry at the University of Potchefstroom provides a diagnostic service on the biochemical level, measuring activity levels of the enzymes involved in Mitochondrial Myopathies.
11. The role of the Muscular Dystrophy Foundation in South Africa
The MDF supports individuals affected by muscular dystrophy and their families by offering emotional support, information - including a series of fact sheets, referrals to genetic counselling and other clinics, formation of support groups, assistance with special equipment, when possible, as well as financial support for research projects in muscular dystrophy in South Africa. Creating public awareness for muscular dystrophy is also an important aspect of our work, since the MDF relies solely on contributions from its members and other donors to provide an on-going support service. Through our newsletter members are kept informed of all the activities and receive national and international research updates. Please contact any office of the MDF if you require information about any of our activities or programmes.
12. Support group or contact person
Please contact the MDF for further information.
13. Where can we find assistance?
Please contact your local MDF office for further information.
13. Where can we find assistance?
Please contact your local MDF office for further information.
General Information: Independent Living Centre (ILC): (011) 482-5476
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Criteria:
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Special Equipment: Phone either ILC or DIC for information on where to get special equipment.
MDF Website: Please visit our MDF website (www.mdsa.org.za) for muscular dystrophy news updates.
14. Please note
The treatments and drugs mentioned in this fact sheet are for information purposes ONLY. Please consult your physician or other health care specialist for information regarding the use of any of the above. The MDF encourages duplication of this fact sheet, under the following condition: that it is duplicated in its entirety - including the MDF logo and full text. Only individuals authorised by the MDF may make changes to this fact sheet (the information "updated by" and "last update" should be completed). Alterations to this fact sheet by any other party are strictly prohibited.
This fact sheet was adapted from the following source(s): Fact sheet(s) of the Muscular Dystrophy Group of Great Britain and Northern Ireland.
Compiled by: MDF-Gauteng Branch
Updated by: MDF-Gauteng Branch
Approved and Released by: National Office of the MDF
Last update: 30 May 2000
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