Kearns-Sayre Syndrome

The Kearns-Sayre Syndrome (KSS) was systematically described for the first time in 1958 and is one of the very rare, genetically determined mitochondrial diseases. The KSS has a core symptomatology with few symptoms that occurs in all patients. In the course of life there are other serious diseases, depending on which tissues are affected by the mitochondrial defects. They have to be treated separately.

What is Kearns-Sayre Syndrome?

The Kearns-Sayre Syndrome affects about 12 out of 100,000 patients. The very rare disease is genetic and manifests itself in a disturbance of the intracellular metabolism. The DNA of the mitochondria in the cells is damaged by mutation at a total of 4977 base pairs. That corresponds to 12 mitochondrial genes.

These defective cells are found in skeletal muscles, external eye muscles, in the liver cells. Since the mutated mitochondria can no longer (correctly) convert the nutrients provided by food intake into energy for the cells, large parts of the muscles and the surrounding tissue are no longer supplied with adenosine triphosphate (ATP).

Unlike other muscle-cell diseases, the ones that are slowly progressing KSS Other tissues are also affected: Depending on which organs are no longer properly supplied with ATP, damage to the heart muscle, muscle weakness, hearing loss, diabetes mellitus, delayed entry into puberty, gastrointestinal problems. The first symptoms are usually diagnosed at the age of 10. There are only several hundred documented cases of the disease worldwide.

causes

The very rare genetic disease occurs only sporadically, so that medicine assumes that it is a matter of spontaneous mutations. Both sexes are equally affected by it. Mitochondrial mutations are passed on from mother to children. Doctors speak of an autosomal recessive inheritance in connection with the inheritance of Kearns-Sayre syndrome.

Symptoms, ailments & signs

The basic symptoms of cooling lubricant appear around the age of 10. The patient has drooping eyelids (ptosis). There are also eye movement disorders (progressive external ophthalmoplagia, CPEO). The pigment disorder of the retina (atypical retinopathia pigmentosa) causes visual disturbances and a visual field restriction. Later on it can lead to progressive muscular atrophy with impaired movement coordination (ataxia). The reflexes are reduced (hyporeflexia) or no longer occur at all (areflexia).

If the heart muscle is damaged, conduction disorders (cardiac arrhythmias) are the result. The impairment of nerve cells leads to sensory disorders in the limbs. In addition, the patients have reduced hearing. Mental impairment up to dementia can also occur in the context of Kearns-Sayre syndrome.

The disturbed hormone balance leads to diabetes mellitus, an underactive thyroid and a growth disorder (short stature). Some patients also develop language and swallowing disorders.

Diagnosis & course of disease

The main symptoms of Kearns-Sayre syndrome are recognizable early on, with most others appearing later as the disease progresses slowly. The CSF analysis shows a protein content of more than 100 mg / dl in KSS patients. The blood level shows increased lactate and pyruvate levels. The mitochondrial structural changes become visible under the electron microscope. The CT shows the calcification of the basal ganglia.

With the help of the EMG, decreased muscle activity can be demonstrated. The stimulus conduction disorders can be determined with the help of the ENG. A biopsy of the skeletal muscles shows a positive result when 1.3 to 10 kb of mitochondrial DNA is disturbed and the typical “ragged-red fibers” can be identified. The electroretinogram makes the "salt and pepper retina" visible.

Cardiomyopathy (irregular heartbeat) is diagnosed using an ECHO and an EKG. However, the medical practitioner treated can only be 100% certain that the examined patient has Kearns-Sayre syndrome if he has examined the entire mitochondrial DNA with the aid of PCR amplification and carried out a sequence analysis of the destroyed mtDNA sequence.

Complications

The Kearns-Sayre syndrome leads to considerable restrictions in everyday life and in the life of the person affected. In most cases, the patients suffer from severe visual disturbances and a limitation of the visual field. Furthermore, complete blindness can occur in the further course. It is not uncommon for the patient to experience heart problems, which can lead to cardiac death.

The sensitivity of the person affected is usually limited and paralysis occurs. Most patients also have dementia or other mental disorders, so that they often have to rely on the help of other people in their everyday lives. This can also lead to speech disorders.

The coordination of movement is also impaired, which leads to movement restrictions or other walking disorders. The quality of life decreases significantly due to the Kearns-Sayre syndrome. In many cases, the parents or relatives of those affected also need psychological treatment to prevent depression or other psychological complaints.

Treatment is carried out with the help of drugs. In many cases, a heart transplant is necessary as it can usually lead to sudden cardiac death. The life expectancy of the patient is severely limited by Kearns-Sayre syndrome.

When should you go to the doctor?

Parents should consult a doctor with their children if there are visual changes in the eyelids. In the event of illness, these suddenly hang down and cannot be changed by intentional muscle tension. The signs of Kearns-Sayre syndrome develop by the age of ten and require medical evaluation and treatment. Eye movement disorders, visual impairments and a reduced reflex reaction are considered unusual and should be clarified. In most cases, the affected person's field of vision is limited. Reduced hearing, cardiac disorders or interruptions in the heart rhythm should be examined by a doctor as soon as possible.

If the child suffers from abnormal sensitivity in the limbs, it needs medical help. Numbness on the skin or hypersensitivity to irritation must be presented to a doctor. If it comes to memory disorders, irregularities in the memory or reduced mental performance, a doctor's visit is necessary.

Medical examinations are advisable in the case of short stature, behavior problems and language disorders. If the child complains of difficulty swallowing, refuses to eat or if there is weight loss, a doctor should be consulted. If there is insufficient fluid intake, the organism is threatened with an undersupply. A doctor must be consulted so that a life-threatening condition is not triggered. Patients with Kearns-Sayre syndrome need a doctor as soon as the symptoms increase.

Therapy & Treatment

The cure for Kearns-Sayre syndrome is not yet possible. The patients generally have a shorter life expectancy, but this can be extended with suitable medical measures. In extreme cases, cardiomyopathy can lead to sudden cardiac death. There is no causal therapy. However, in most of the cooling lubricant patients, highly concentrated coenzyme Q10 (ubiquinone) can improve their condition. Usually a dose of 30 to 260 mg is consumed orally.

Alternatively, 90 to 270 mg / day of idebenone can be taken. The agents improve mitochondrial function in the brain and skeletal muscles. For other mitochondrial defects, carnitine or creatine are also prescribed, for example. Otherwise, treatment can only be given symptomatically. Regular visits to the cardiologist help in the treatment of chronic cardiac arrhythmias. In some cases a pacemaker must be used.

If the condition is particularly bad, a heart transplant may even be indicated. The hearing loss can be compensated for at least for a certain period of time with a suitable hearing aid. Regular ophthalmologic visits reduce the risk of eye complications. If Kearns-Sayre syndrome is present, the prognosis depends on the severity of the disease, that is, on how many organs are involved in the disease process, and on the proportion of abnormal mtDNA present in each of them.

Outlook & forecast

Although Kearns-Sayre syndrome is rare, the prognosis for the disorder is poor. The cause is a genetic defect that cannot and must not be treated. For legal reasons, scientists and medical professionals are not allowed to change human genetics. This cannot cure the disorder. Symptomatic treatment takes place, which can only alleviate the existing symptoms.

The patient is exposed to long-term therapy, which is associated with various stresses and side effects. As soon as the applied treatment is interrupted or independently terminated, a relapse of the complaints is to be expected. Many of the existing complaints cannot be treated despite all efforts and medical options.

In the case of mental impairments and disorders of the brain, there are usually no therapeutic approaches to improve health. In these cases, the patient is accompanied with the best possible means and a nurse is provided. Coping with everyday life is usually not possible. Due to the large number of disorders that are triggered by the syndrome, it can lead to a strong emotional burden for the person affected and their relatives. Psychological disorders can break out and lead to a further deterioration of the overall situation. This must be taken into account when making a forecast.

prevention

Prevention is not possible with Kearns-Sayre syndrome because it is a genetic disease. The exact genesis has not yet been clearly clarified. However, it is possible, with the help of suitable specialist methods, to recognize new symptoms of the severe chronic disease early enough and to treat them in good time.

Aftercare

In most cases, those affected with Kearns-Sayre syndrome have no special or direct follow-up options available, so that the patient is definitely dependent on a quick and, above all, early diagnosis of the disease. As soon as the first signs and symptoms appear, the person affected should therefore consult a doctor in order to prevent the symptoms from worsening.

Since Kearns-Sayre syndrome is a genetic disease, genetic testing and counseling should be carried out if you want to have children to prevent the disease from recurring. Most people affected by Kearns-Sayre syndrome are dependent on medication.

It is always important to take it regularly and to use the correct dosage so that the symptoms can be relieved permanently. A cardiologist should also be visited regularly so that the condition of the heart can be permanently checked. In the worst case, this can lead to sudden cardiac death, so that life expectancy is reduced in many cases by the syndrome. The further course of this disease depends heavily on the time of diagnosis, so that no general prediction can be made about it.

You can do that yourself

In the case of Kearns-Sayre syndrome, the most important self-help measure is to optimally adapt the medication to the living conditions. Since those affected are at increased risk of sudden cardiac death, it is also important to watch out for unusual symptoms and complaints.

If heart pains, shortness of breath, pain and other signs of the disease become noticeable, the emergency doctor must be alerted immediately. In less severe cases, patients only need to take it easy. Exhausting physical activities should be avoided, as well as stress and stimulants such as alcohol, caffeine or nicotine. The hearing loss can be compensated for with a suitable hearing aid. The eyesight can at least be stabilized through regular visits to the ophthalmologist.

If you are in particularly poor health, you will need a heart transplant. In preparation for this procedure, the patient must change their diet and inform the doctor that they are taking any medication. Illnesses, allergies or ailments that the doctor may not yet know about must also be clarified before the procedure. After the operation, the patient needs rest and bed rest, accompanied by close medical care. What other measures the person concerned can take depends on which organs are involved in the disease process.