Kearns-Sayre syndrome (KSS) was first systematically described in 1958 and is one of the very rare genetic mitochondrial disorders. KSS has a core symptomatology with few symptoms that occurs in all patients. During life, other severe diseases are added depending on which tissues are affected by the mitochondrial defects. They must be treated separately.
What is Kearns-Sayre syndrome?
Kearns-Sayre syndrome affects about 12 in 100,000 patients. The very rare disorder is genetic and manifests as a disorder of intracellular metabolism. The DNA of the mitochondria located in the cells is damaged at a total of 4977 base pairs by mutation. This corresponds to 12 mitochondrial genes. These defective cells are located in skeletal muscles, external eye muscles, in liver cells. Since the mutated mitochondria can no longer (properly) convert the nutrients provided by food intake into energy for the cells, large parts of the muscles and surrounding tissues are no longer supplied with adenosine triphosphate (ATP). In contrast to other muscle-cell diseases, slowly progressing KSS also affects other tissues: Thus, depending on which organs are no longer properly supplied with ATP, damage to the heart muscle, muscle weakness, hearing loss, diabetes mellitus, delayed onset of puberty, gastrointestinal problems occur. The first symptoms are usually diagnosed in the 10th year of life. There are only several hundred documented cases of the disease worldwide.
Causes
The very rare genetic disorder occurs only sporadically, so medical science assumes that it is caused by spontaneous mutations. It affects both sexes equally. Mitochondrial mutations are passed on from mother to child. Medical experts speak of autosomal recessive inheritance in connection with the inheritance of Kearns-Sayre syndrome.
Symptoms, complaints, and signs
The basic symptoms of KSS appear around the age of 10. The patient has drooping eyelids (ptosis). Eye movement disorders (progressive external ophthalmoplagia, CPEO) are also evident. The pigmentary disorder of the retina (atypical retinopathia pigmentosa) causes visual disturbances and a reduced field of vision. Later, there may be progressive muscle atrophy with disturbances in movement coordination (ataxia). Reflexes are reduced (hyporeflexia) or do not 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 disturbances in the limbs. In addition, the patients still have a reduced hearing ability. Mental impairment up to dementia can also occur in the context of Kearns-Sayre syndrome. Due to the disturbed hormone balance, diabetes mellitus, hypothyroidism and growth disturbance (short stature) occur. Some patients also develop speech and swallowing disorders.
Diagnosis and course of the disease
The main symptoms of Kearns-Sayre syndrome are apparent early, with most others coming later as the disease progresses slowly. CSF analysis reveals protein levels greater than 100 mg/dl in KSS patients. Blood levels show elevated lactate and pyruvate. Electron microscope reveals mitochondrial structural changes. CT shows calcification of the basal ganglia. With the help of EMG, decreased muscle activity can be detected. Stimulus conduction disorders can be detected with the help of ENG. A biopsy of the skeletal muscles shows a positive result if 1.3 to 10 kb of the mitochondrial DNA are disturbed and the typical “ragged-red fibers” are recognizable. Electroretinogram reveals the “salt and pepper retina”. Cardiomyopathy (cardiac arrhythmia) is detected by ECHO and ECG. One hundred percent certainty that the patient being studied has Kearns-Sayre syndrome, however, is not available to the treating physician until he or she has used PCR amplification to examine all mitochondrial DNA and performed sequence analysis of the destroyed mtDNA sequence.
Complications
Kearns-Sayre syndrome results in significant limitations in the daily life and living of the affected individual.In most cases, patients suffer from severe visual disturbances and a restriction of the field of vision. Furthermore, complete blindness may occur in the further course of the disease. It is not uncommon for patients to experience heart problems, which can lead to cardiac death. The sensitivity of the affected person is also usually impaired and paralysis occurs. Most patients also exhibit dementia or other mental disorders, so that they are not infrequently dependent on the help of other people in their daily lives. Speech disorders may also occur. Coordination of movement is also impaired, leading to restricted movement or other walking disorders. The quality of life decreases considerably due to Kearns-Sayre syndrome. In many cases, the parents or relatives of the affected person also need psychological treatment to prevent depression or other psychological complaints. The treatment is carried out with the help of medication. In many cases, a heart transplant is necessary, as otherwise sudden cardiac death may occur. The patient’s life expectancy is significantly limited by Kearns-Sayre syndrome.
When should you see a doctor?
Parents should see a doctor with their children if there are visual changes in the eyelids. These droop suddenly in the case of the disease and cannot be changed by deliberate muscle tension. The signs of Kearns-Sayre syndrome develop in the tenth year of life and must be medically examined as well as treated. Disturbances in eye movements, impaired vision, and decreased reflex response are considered unusual and should be investigated. In most cases, the affected person’s field of vision is limited. Reduced hearing, disturbances in cardiac activity, or interruptions in heart rhythm should be evaluated by a physician as soon as possible. If the child suffers from abnormalities of sensitivity in the limbs, he or she needs medical attention. Numbness of the skin or hypersensitivity to a stimulus must be presented to a doctor. If there are memory disorders, irregularities in memory or reduced mental capacity, a visit to the doctor is necessary. In case of short stature, behavioral abnormalities and speech disorders, medical examinations are advisable. If the child complains of difficulty swallowing, refuses to eat or loses weight, a doctor should be consulted. If there is insufficient fluid intake, the organism is at risk of malnutrition. To avoid triggering a life-threatening condition, a physician must be consulted. Patients of Kearns-Sayre syndrome need a doctor as soon as an increase in symptoms occurs in the further course.
Treatment and therapy
Cure for Kearns-Sayre syndrome is not yet possible. Patients generally have a shorter life expectancy, but this is prolonged with appropriate medical measures. In extreme cases, sudden cardiac death may result from the cardiomyopathy. There is no causative therapy. However, most KSS patients can be improved with the help of highly concentrated coenzyme Q10 (ubiquinone). 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, for example, is also prescribed. Otherwise, only symptomatic therapy can be given. Regular visits to the cardiologist help in the treatment of chronic cardiac arrhythmias. In some cases, a pacemaker must be inserted. In particularly poor condition, even a heart transplant may be indicated. Hearing loss can be compensated for at least some time with a suitable hearing aid. Regular visits to the ophthalmologist reduce the risk of eye complications. In the presence of Kearns-Sayre syndrome, the prognosis depends on the severity of the disease, that is, how many organs are involved in the disease process and the proportion of abnormal mtDNA present in each.
Outlook and prognosis
Although Kearns-Sayre syndrome is rare, the prognosis of the disorder is unfavorable. It is caused by a genetic defect that cannot and should not be treated.For legal reasons, scientists and medical doctors are not allowed to change the genetics of human beings. Thus, the disorder cannot be cured. Symptomatic treatment takes place, which can only alleviate the existing symptoms. The patient is subjected to long-term therapy, which is associated with various stresses and side effects. As soon as the applied treatment is interrupted or stopped on one’s own responsibility, a relapse of the complaints is to be expected. Many of the existing complaints are not treatable despite all efforts and medical possibilities. In the case of mental impairments as well as disorders of the brain, there are usually no therapeutic approaches to achieve an improvement in health. In these cases, the patient is accompanied to the best of his or her ability and a caregiver is provided. Coping with everyday life is usually not possible. Due to the multitude of disorders triggered by the syndrome, there can be a strong emotional burden for the affected person as well as their relatives. Psychological secondary disorders can break out and lead to a further deterioration of the overall situation. This must be taken into account when making a prognosis.
Prevention
Prevention is not possible in Kearns-Sayre syndrome because it is a genetic disorder. The exact genesis has not yet been clearly established. However, with the help of appropriate specialist methods, it is possible to detect new symptoms of the severe chronic disease early enough and to treat them in time.
Follow-up
In most cases, the person affected by Kearns-Sayre syndrome does not have any special or direct options for follow-up care, so the patient is definitely dependent on a quick and, above all, early diagnosis of the disease. Even at the first signs and symptoms, the affected person should therefore consult a doctor in order to prevent a further worsening of the symptoms. Since Kearns-Sayre syndrome is a genetic disease, genetic testing and counseling should be performed if the patient wishes to have children in order to prevent the recurrence of the disease. Most people affected by Kearns-Sayre syndrome are dependent on taking medication. It is always important to ensure that the medication is taken regularly and in the correct dosage so that the symptoms can be permanently alleviated. A cardiologist should also be consulted regularly so that the condition of the heart can be permanently checked. In the worst case, sudden cardiac death can occur, so that life expectancy is reduced in many cases due to the syndrome. The further course depends with this illness strongly on the time of the diagnosis, so that about it no general prediction can be made.
What you can do yourself
In Kearns-Sayre syndrome, the most important self-help measure is to optimally adapt medication to life circumstances. Because affected individuals are at increased risk for sudden cardiac death, it is also important to watch for unusual symptoms and discomfort. If heart palpitations, shortness of breath, pain and other signs of the disease become apparent, the emergency physician must be alerted immediately. In less severe cases, patients simply need to take it easy. Strenuous physical activity should be avoided, as should stress and stimulants such as alcohol, caffeine or nicotine. Hearing loss can be compensated for with a suitable hearing aid. Vision can at least be stabilized by regular visits to the ophthalmologist. If the patient is in particularly poor health, a heart transplant must be performed. In preparation for this procedure, the patient must change his or her diet and inform the doctor about taking any medications. Any illnesses, allergies, or medical conditions that the physician may not yet know about must also be clarified prior to the procedure. After the operation, the patient requires rest and bed rest, accompanied by close medical care. What other measures the patient can take depends on which organs are involved in the disease.
