Mitochondriopathies are diseases of the mitochondria. These are located in almost every cell of the body and supply the body with energy. The manifestations and symptoms of mitochondriopathy can vary widely.
What is mitochondriopathy?
Mitochondria are small cell organelles. Important metabolic processes take place in them. As part of the respiratory chain, for example, energy is obtained in the form of adenosine triphosphate (ATP). In mitochondriopathy, there is a disorder in the proteins of the cell organelles. As a result, not as much energy can be obtained. In particular, the brain and eyes are affected in mitochondriopathy. The disease can be acquired or congenital. However, there are also smooth transitions between the two forms.
Causes
Mitochondriopathy is caused by damage to or malfunction of mitochondria. Hereditary mitochondriopathy is caused by gene mutations. These affect the enzymes and metabolism of the mitochondrion. The gene defects are already present at birth. Mutations in the DNA of the mitochondria are inherited only through the mother. If, on the other hand, the mitochondriopathy is nuclear coded, the disease can be inherited autosomal dominant, autosomal recessive or X-linked. The first symptoms usually appear in childhood or adolescence. In acquired mitochondriopathies, it is suspected that the cell organelles lose their function due to environmental influences. However, it is not yet clear which environmental influences these are. Frequently, mixed forms also occur. This means that there is a hereditary predisposition, but it is only activated by environmental influences. The main task of the mitochondria is the production of energy by fatty acid combustion, the degradation of acetyl-CoA and by oxidative phosphorylation. Due to mutations, there are disturbances during the citrate cycle or during fatty acid oxidation. As a result, less energy is available. Because the respiratory chain enzymes that may be impaired in mitochondriopathy are tissue-specific, only one or two organs may be affected by the disease.
Symptoms, complaints, and signs
More than fifty enzymes may be affected by mitochondriopathy within mitochondria. Because each of these enzymes performs different tasks, symptoms are correspondingly varied. However, there are typical constellations of symptoms. In chronic progressive external ophthalmoplegia (CPEO), eye movement disorders occur. The eyelids droop (ptosis). This form of mitochondriopathy does not begin until the age of 20 to 40 years. If there is also paralysis of the external eye muscles and polyneuropathies or growth disorders, there is probably ophthalmoplegia plus (CPEOplus). This form often transitions smoothly into Kearns-Sayre syndrome (KSS). In addition to the symptoms of CPEO, cardiac muscle disease or retinal changes also occur here. The disease of the heart muscle is characterized by conduction disorders. Another form of mitochondriopathy is myoclonus epilepsy with ragged red fibers (MERRF). It results in myoclonic epilepsy with progressive dementia and muscle weakness. The disease usually begins between the ages of 5 and 15. Patients with MELAS syndrome are often small in stature and suffer from migraine and/or diabetes mellitus. The onset of the disease here is also between 5 and 15 years of age. The name MELAS syndrome refers to the typical clinical symptoms: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Leber’s optic atrophy (LHON) is optic nerve damage with retinal changes. In this case, painless vision loss occurs after the age of 20. Leigh syndrome manifests in the second or first year of life. The affected children are mentally retarded and suffer from muscle weakness. In addition, damage to the brainstem occurs, manifested by dysphagia or eye movement disorders.
Diagnosis and course of the disease
Laboratory findings provide information about mitochondriopathy. Here, lactic acidosis becomes apparent. This is an overload of lactic acid caused by the disturbance in the citrate cycle. As part of metabolic diagnostics, the organic acids in the urine and the amino acids in the blood serum are also determined.If the suspicion of a mitochondriopathy is confirmed, a muscle sample can be taken by means of a muscle biopsy. The diagnosis can be confirmed by the detection of so-called ragged red fibers. Detection is performed in the Gömöri trichrome stain.
Complications
As a result of mitochondriopathy, affected individuals usually suffer from various medical conditions. In most cases, the disease causes the eyelids of affected individuals to droop severely, resulting in decreased aesthetics. This can have a negative effect on self-esteem and also lead to inferiority complexes. As a rule, the quality of life is considerably reduced by mitochondriopathy. Likewise, it is not uncommon for growth disorders to occur, and furthermore, paralysis of the eye muscles. Diseases of the heart muscle also occur, which in the worst case can be fatal. Those affected appear tired and listless and not infrequently suffer from migraines. The risk of a stroke also increases enormously, so that the life expectancy of the patient is also significantly reduced by the mitochondriopathy. Muscle weakness occurs and with it a reduced ability to work under pressure. Not infrequently, swallowing difficulties also lead to difficulties in taking food and liquids. A causal treatment of mitochondriopathy is not possible. Patients are therefore dependent on a special diet and must avoid stimulating activities. This results in various restrictions in everyday life.
When should one go to the doctor?
Irregularities in eye movements are signs of a present disorder. If the complaints persist over a longer period of time or increase in intensity, a visit to the doctor must be made. Since the disorder has its onset at the age of 20, appearing symptoms are alarming, especially in people in young adulthood. If there are visual changes in the shape of the eyes, there is cause for concern. In case of drooping eyelids or problems with vision triggered by them, a doctor is needed. If the affected person suffers from paralysis of the eye muscles, a doctor should be consulted. Growth disturbances as well as inconsistencies of the heart rhythm are further indications of the organism of a health impairment. If the affected person has the feeling that the activity of the heart is not sufficient or if there is shortness of breath, a visit to the doctor is advisable. General muscle weakness, low performance and problems with memory should be clarified by a doctor. Swallowing disorders, short stature or an existing diabetes should be discussed with a doctor. If the affected person notices further irregularities, a check-up is recommended in order to intensively check the general state of health. Reduced vision from young adulthood onwards may be due to retinal damage caused by mitochondriopathy. Affected individuals are therefore strongly advised to consult a physician as well as an optometrist.
Treatment and therapy
Mitochondriopathies are usually hereditary, so no causative therapy is possible. Energy production is severely limited in mitochondriopathy. Therefore, those affected should consume as much energy as possible in the form of fats and glucose. Adequate intake of minerals and water should also be ensured. Any physical condition that results in increased energy consumption should be avoided if possible. This includes sports, for example. But increases in temperature are also associated with increased energy requirements. Fever should therefore always be reduced in patients with mitochondriopathy. Seizures also consume a lot of energy. Consistent therapy is required here. However, drugs that inhibit the respiratory chain must not be used. The respiratory chain is already impaired in mitochondriopathy anyway and cannot tolerate any further restrictions. Very severe lactic acid overload can also be treated with buffer substances. Supportive vitamins and cofactors can be used.
Outlook and prognosis
Patients with mitochondriopathy cannot be cured to date. A prognosis for those affected depends primarily on how early the first of the typical symptoms appear, how rapidly the disease progresses, and also how marked the seizures are.However, life expectancy and quality of life can be improved by an adapted therapy. Whether a therapy helps and which treatment is indicated for mitochondriopathy is very different for each patient and also requires constant care by specialists in this disease. The symptoms of the disease usually appear in adolescence or already in early adulthood. Nevertheless, infants can also be affected by the disease. As a rule, the earlier affected persons become ill, the more rapidly the disease progresses. In addition, the symptoms are often more severe than in patients who develop the disease much later. In these cases, the disease usually progresses more slowly and with much milder symptoms. However, very severe and rapid courses are also possible in younger adults. Since the last years, the possibilities of a therapy have increased significantly. Newly developed methods of analyzing the genetic material are expected to improve the treatment of many mitochondrial diseases in the coming years.
Prevention
In a large number of cases, mitochondriopathy is hereditary. Therefore, there is no effective prevention. However, some mitochondriopathies are also favored by environmental influences. Since it has not yet been conclusively clarified here which environmental influences can have a negative effect, there are currently no prevention suggestions here either.
Follow-up
Treatment of mitochondriopathies must be continued permanently. Follow-up care focuses on providing the necessary therapeutic support to those with the disease. In addition, the intake of medications must be regularly reviewed and adjusted. Patients must consult their physician at regular intervals. The current state of health is discussed with the physician. Any complaints must be clarified and alleviated by adjusting the therapy. The follow-up care also includes a constant adjustment of the diet. Since metabolic fluctuations occur in mitochondriopathy, various values, such as pulse and blood pressure, must be measured again and again. Accompanying this, the treatment with supplements must be monitored. The responsible nutritionist checks the effectiveness of the prescribed vitamins and adjusts the dose if necessary. The measures that are useful and necessary in the course of follow-up care depend on the respective symptom picture. In principle, neuromuscular symptoms must be monitored in order to detect complications at an early stage. Further follow-up steps depend on the usually very variable course of the disease. Mitochondriopathies progress rapidly, which is why most patients require medical attention several times a month. In severe cases, ongoing therapy is necessary.
What you can do yourself
Mitochondriopathy cannot be treated causally. However, symptomatic therapy can be supported by some strategies and measures. If fever occurs, appropriate measures must be taken to lower the body temperature. Classic methods such as cooling compresses or yogurt wraps have proven effective. A short walk in the fresh air can also help, provided the outside temperature is not too low. In the case of seizures, a doctor should be consulted in any case. Accompanying first aid measures should be taken to alleviate the risk of injury from falls on the one hand and the cramps themselves on the other. If possible, the affected person should lie on his or her back and soothe the cramping part of the body with gentle massage. If the cramp occurs in several limbs, heat treatments can help. Usually, the discomfort subsides after a few minutes if the affected muscles are consistently soothed and relaxed. A good household alternative is St. John’s wort oil. The herbal remedy helps especially with mild cramps in the muscles and contributes overall to relaxation. Supporting vitamins and minerals help. If the complaints last longer than usual or unusual symptoms occur, a doctor should be consulted.
