Mitochondrial

Mitochondriopathy: description

What are mitochondria?

By mitochondriopathy, physicians understand a disease of certain structures of the body’s cells, the mitochondria. These tiny “cell organelles” are also called “power plants of the cell”. They occur in almost all human cells. In them metabolic processes such as the so-called respiratory chain take place. Through this process, the body uses about 90 percent of body energy, for example, sugar (glucose) or fatty acids.

In mitochondrial disease, the proteins (proteins) involved in the respiratory chain are not functional. Therefore, only relatively little energy is gained. The reason for this is a change in the genetic material (mutation). This especially affects organs that require a lot of energy. These include, among other things, the brain or the eye muscles.

Occurrence and frequency

The first symptoms of mitochondrial disease occur in childhood and adolescence, sometimes even in early adulthood. It is estimated that out of 100,000 people, approximately twelve suffer from mitochondriopathy.

Mitochondriopathy: symptoms

There are different forms of mitochondriopathy, which differ in their symptoms. According to the symptoms, mitochondriopathies are divided into different syndromes. The word syndrome refers to signs of disease that occur simultaneously and are related.

Common symptoms of patients with various mitochondriopathies are common:

• short stature
• Exercise-dependent muscle weakness
• Ocular palsies
• Diabetes mellitus
• Seizures (epilepsy)

The following syndromes are only a part of possible mitochondriopathies, but other syndromes are less common:

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 occurs when the body has to provide a lot of energy without the mitochondria respiratory chain working together. It is the cause of stroke-like episodes that, like a true stroke, are associated with paralysis. Reason is a reduced blood circulation and a lack of oxygen in the brain. Most of these symptoms disappear as soon as lactic acidosis is treated.

MERRF syndrome

The abbreviation “MERRF” stands for myoclonus epilepsy with “ragged-red-fibers”. As a myoclonus doctors refer to an involuntary twitching muscles. “Red-Ragged-Fibers” describe muscle cells with swollen mitochondria, which the pathologist finds in a tissue sample under the microscope in a mitochondriopathy of this kind. The patients often suffer from movement and balance disorders, usually a severe epilepsy is in the foreground of the complaints.

Kearns-Syre syndrome

In this form of mitochondrial disease, patients primarily suffer from eye damage such as paralysis of the eye muscles or retinal changes. Also heart muscle damage occur frequently. Regular cardiologist examinations are important for these patients. In many people affected the hormone balance is disturbed, which manifests itself in the form of diseases such as diabetes mellitus or hypothyroidism.

LHON

The abbreviation “LHON” stands for Leber’s hereditary optic neuropathy – a disease of the optic nerve (optic nerve).

Mitochondrial disease: causes and risk factors

Changes in the mitochondrion as a cause

In mitochondriopathy, the so-called mitochondrial respiratory chain is altered. It consists of various proteins (proteins) and serves as the main energy supplier of the body. The genome contains information about how these proteins should be shaped and functioned. If damage occurs there (mutations), the proteins are not produced or built incorrectly. The respiratory chain then does not work properly and the energy supply 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.

How changes happen

Mitochondrial disease can be inherited as well as sporadic, without hereditary preoccupation. In most cases, mitochondrial disorders have a sporadic change. If they are inherited, the mutation usually starts from the mother. Since the paternal sperm leaves its mitochondria behind when fertilizing the egg, later all mitochondria of the child come from the egg.

In addition, there are mitochondria in an ovum with various genetic information that can mutate only partially (heteroplasmy). Depending on how many mitochondria of the egg cell were changed and in which organs they occur in the child, corresponding symptoms and organ involvement show.

Mitochondriopathy: examinations and diagnosis

Mitochondriopathy: First steps to diagnosis

To diagnose “mitochondriopathy,” your doctor will first ask you in detail about the history of the disease (anamnesis). He will ask you the following questions:

• When did the symptoms first appear?
• Are the symptoms stronger under stress?
• Do you experience muscle aches?
• Do epileptic seizures occur?
• Is a family member suffering from similar symptoms?
• Is there a hereditary disease in your family?

Only if the symptoms confirm the suspicion of mitochondriopathy, further investigations are carried out. These should take place in specialized centers.

Blood tests are used to determine metabolites, such as milk sugar (lactate). If it is suspected that certain organs have been affected by mitochondrial disease, the doctor may initiate an electrocardiogram (ECG) or a cardiac encephalogram. The ophthalmologist makes an eye test and assesses the fundus. Magnetic resonance imaging (MRI) can detect damage to the brain.

In the further course, the concentrations of the hormones in the body should be regularly determined, since in patients with mitochondriopathy more frequent hormonal diseases such as diabetes mellitus or hyperparathyroidism (parathyroid disease) occur.

A muscle biopsy provides information

The doctor can safely diagnose mitochondrial disease by taking a tissue sample from a muscle (muscle biopsy) under local anesthesia. Subsequently, a pathologist examines the sample under a microscope. In addition, experts can analyze the genome (DNA) of muscle cells and track down the mutation.

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Families should visit a human genetic counseling center after completing their diagnosis. There, the exact mutation is determined and set up a family tree. In this way, further affected persons can be identified and the risk for possible offspring can be estimated.

Mitochondriopathy: treatment

Mitochondrial disease is not curable. The aim of the treatment is to alleviate the symptoms and prevent possible complications (symptomatic therapy). Depending on which syndrome the patient suffers from and which symptoms are the most important, the doctor adjusts the treatment.

Drug treatment options

Some medications support the work of the respiratory chain in the mitochondria, such as so-called co-factors, antioxidants, vitamin B1 or vitamin B2. Other medications (anticonvulsants) work against seizures (epilepsy) and in many cases prevent the recurrence of a seizure. For example, carbamazepine or lamotrigine are helpful; valproate must be avoided because of severe side effects associated with mitochondriopathy. If movement disorders occur, the physician may administer botulinum toxin with muscle stiffness dopamine or with increased muscle activity. Stroke-like episodes are usually treated with cortisone.

Further treatment options

Especially endurance sports such as running or cycling are helpful. It is important that patients with mitochondriopathy stay below their maximum exercise limit during exercise.

A high-fat and low-carbohydrate diet (ketogen) can also help stabilize epilepsy. The affected person has to eat enough calories. The patient first learns the ketogenic diet in the hospital, as it must pay close attention to the ratio of fats to carbohydrates. Later he can continue the diet at home.

Physio-, ergo and speech therapy are used to improve the function of the muscles.

Mitochondriopathy: disease course and prognosis

Depending on the syndrome, the first symptoms of mitochondrial disease usually appear in adolescence or early adulthood. But infants can already be affected. The sooner the children get sick, the faster mitochondrial disease usually progresses. In addition, the symptoms are then often stronger than in patients who become ill later. With them, the disease usually runs slower and with milder symptoms. However, fast and violent courses in young adults are possible.

Mitochondrial disease can not be cured. The prognosis depends on how early the first symptoms appear, how fast the disease progresses and how severe the seizures are. Life expectancy and quality can be improved by optimal therapy. If and which therapy at one Mitochondrial helps, is very different from patient to patient and requires constant care by specialists.