Brief overview
- Symptoms: Depending on which mitochondrial proteins are altered and how severe: muscle weakness, metabolic disorders such as diabetes, seizures, blindness.
- Causes and risk factors: alterations (mutations) in genes for proteins involved in metabolic processes in cellular power plants, either through maternal inheritance or new mutation
- Diagnosis: Medical history, previous family history, physical examinations, blood tests, muscle cell biopsy, genetic analysis
- Treatment: Only treatment of symptoms possible, cure is not possible according to current research; medication, diets, physiotherapy, occupational therapy or speech therapy (depending on symptoms)
- Prognosis: The earlier the disease appears, the more severe and severe the course is usually; life expectancy and quality of life can be significantly improved with targeted therapy
What is mitochondriopathy?
What are mitochondria?
These tiny “cell organelles” are also known as the “power plants of the cell”. They are found in almost all human cells. Metabolic processes such as the so-called respiratory chain take place in them. Through this process, the body obtains about 90 percent of the body’s energy from sugar (glucose) or fatty acids, for example.
In mitochondriopathy, the proteins involved in the respiratory chain are not functional. Therefore, relatively little energy is obtained. The reason for this is a change in the genetic material (mutation). This primarily affects organs that require a lot of energy. These include the brain or the eye muscles.
Occurrence and frequency
The first symptoms of mitochondriopathy appear in childhood and adolescence, sometimes in early adulthood. It is estimated that about twelve out of every 100,000 people suffer from mitochondriopathy.
What are the symptoms?
According to the symptoms, mitochondriopathies are divided into different syndromes. The word syndrome refers to signs of disease that occur simultaneously and are interrelated.
Common symptoms of patients with different mitochondriopathies are often:
- Short stature
- Exercise-induced muscle weakness
- Eye muscle paralysis
- Diabetes mellitus
- Seizures (epilepsy)
The syndromes listed below represent only a subset of possible mitochondriopathies, but other syndromes occur less frequently.
MELAS syndrome
The abbreviation “MELAS” stands for “mitochondrial encephalopathy, lactic acidosis and stroke-like episodes”. In MELAS syndrome, patients suffer from seizures and dementia. Encephalopathy describes diseases of the brain. Lactic acidosis (a “lactic acidosis”) occurs when the body needs to provide a lot of energy without the mitochondria’s respiratory chain cooperating.
MERRF Syndrome
The acronym “MERRF” stands for “Myoclonus Epilepsy with Ragged-Red Fibers.” Myoclonus is what doctors call involuntary twitching muscles. “Red-ragged fibers” describe muscle cells with swollen mitochondria that pathologists find in a tissue sample under the microscope in a mitochondriopathy of this type. Patients often suffer from movement and balance disorders, and severe epilepsy is usually at the forefront of their symptoms.
Kearns-Syre syndrome
In this form of mitochondriopathy, patients suffer primarily from eye damage such as paralysis of the eye muscles or retinal changes. Damage to the heart muscle also occurs more frequently. For these patients, regular examinations by a cardiologist are important.
In many of those affected, hormone balance is disturbed, which manifests itself in the form of diseases such as diabetes mellitus or hypothyroidism.
LHON
What is the life expectancy in mitochondriopathy?
The life expectancy and quality of life of those affected can be improved by an optimal therapy adapted to each case. Whether and which therapy helps in mitochondriopathy varies greatly from patient to patient and requires constant care by specialists.
Since the syndromes are quite different and range from mild to severe symptoms, there is no general statement on the life expectancy of those affected.
Causes and risk factors
Changes in the mitochondrion as a cause
In the “cellular power plants”, the mitochondria, a number of metabolic processes take place, most of which serve to provide energy for the cell from sugar or fat.
How these proteins are to be built and shaped is stored in the genes, the genetic material of the cell, and predominantly in parts of the genetic material that are only present in the mitochondria. If damage occurs to the genes for these proteins (mutations), the proteins are not produced at all or are built incorrectly. This then has corresponding effects on their function.
The complex metabolic processes, such as the respiratory chain, then do not function properly and the supply of energy is disturbed. Accordingly, the effects of mitochondriopathy primarily affect organs that require a lot of energy. These include, for example, the brain, the eye muscles or the skeletal muscles.
In the meantime, science has identified more than 1700 genes in the cell nucleus that play a role in the mitochondria. More than 300 of these are probably related to various mitochondriopathies.
How changes arise
If it is inherited, the mutation usually originates from the mother. Since mitochondria from the paternal sperm are degraded during fertilization of the egg cell, all mitochondria of the child later usually originate from the egg cell.
In addition, there are several mitochondria with different genetic information in an egg cell, which sometimes mutate only partially (heteroplasmy). There are several hundred thousand mitochondria in an oocyte. In the course of the embryo’s development, the mitochondria are distributed to different cells and only then duplicate.
Therefore, depending on how many mitochondria of the egg cell were altered and in which organs they are present in the child – and which proteins are affected – different symptoms and organ involvement are possible.
Examinations and diagnosis
Mitochondriopathy: First steps to diagnosis
To make the diagnosis of “mitochondriopathy,” your doctor will first ask you in detail about your medical history (anamnesis). In doing so, he or she will ask you the following questions, among others:
- When did the symptoms first occur?
- Are the symptoms more severe with exertion?
- Do you experience muscle pain?
- Do epileptic seizures occur?
- Do any of your family members suffer from similar symptoms?
- Are there any hereditary diseases in your family?
Only if the symptoms substantiate the suspicion of a mitochondriopathy, the doctor will carry out further examinations. These are then most likely to take place in specialized centers.
An ophthalmologist performs an eye test and evaluates the back of the eye. Magnetic resonance imaging (MRI) can be used to detect damage to the brain.
In the further course, the concentrations of hormones in the body are usually determined regularly, since patients with mitochondriopathy frequently have hormonal diseases such as diabetes mellitus or “hyperparathyroidism” (disease of the parathyroid glands).
New diagnostic methods
Mitochondriopathy can be reliably diagnosed by the physician taking a tissue sample from a muscle (muscle biopsy) under local anesthesia. A pathologist then examines the sample under a microscope and in many cases sees characteristic changes in the mitochondria.
With a molecular biological analysis of the genetic material (DNA) from the sample of the muscle cells, mutations can then be visualized. This method has meanwhile gained in importance.
Help at a human genetic counseling center
For families of affected persons, advice is available at a human genetic counseling center once the diagnosis has been established. There, the exact mutation is determined and a family tree is drawn up. In this way, it may be possible to identify other affected individuals and also to estimate the risk of inheritance to possible offspring.
Treatment
Mitochondriopathy is not curable. The goal of treatment is to alleviate symptoms and prevent possible complications (symptomatic therapy). Depending on which syndrome the patient is suffering from and which symptoms are the main focus, the physician will adjust the treatment.
However, as science gains a better understanding of the causes and interrelationships of the various mitochondriopathies, there are increasingly new approaches to treatment. There is now a drug on the market specifically to treat LHON syndrome, called idebenone.
Drug treatment options
Other drugs (anticonvulsants) act against seizures (for example, in epilepsy) and in many cases prevent the recurrence of a seizure. Carbamazepine or lamotrigine, for example, are helpful. The antiepileptic drug valproate is not suitable for use in mitochondriopathy because of severe side effects.
If movement disorders occur, the physician often prescribes dopamine for muscle stiffness or botulinum toxin for increased muscle activity. Stroke-like episodes are usually treated with cortisone.
Other treatment options
Above all, endurance sports such as running or cycling are helpful. It is important that patients with mitochondriopathy stay below their maximum stress limit when exercising.
A high-fat and low-carbohydrate diet (= ketogenic) helps in many cases to stabilize an occurring epilepsy. In doing so, the affected person must consume a sufficient number of calories.
Physical therapy, occupational therapy as well as speech therapy are used to improve the function of the musculature.
Course of the disease and prognosis
The first symptoms of mitochondriopathy usually appear in adolescence or early adulthood, depending on the syndrome. However, depending on the severity and type of mutation(s), infants are also affected.
The earlier the children become ill, the faster the mitochondriopathy usually progresses. In addition, the symptoms are often more severe than in patients who develop the disease later. In them, the disease usually progresses more slowly and with milder symptoms. However, rapid and severe courses are also possible in young adults.
According to the current state of research, mitochondriopathy cannot be cured. The prognosis depends on how early the first symptoms appear, how quickly the disease progresses, and how severe the seizures are.
As new gene sequencing methods improve our understanding of the causes of the various mitochondriopathies, more specific therapies are becoming available. A specific drug (idebenone) has already been approved for LHON, and studies to date have shown that it is able to preserve the vision of those affected.