Leigh syndrome is a hereditary disease. It is one of the mitochondriopathies.
What is Leigh syndrome?
Leigh syndrome is the name given to a hereditary disorder in which there is a disturbance in mitochondrial energy metabolism. The disease also goes by the names Leigh’s disease, Leigh’s disease, and subacute necrotizing encephalomyelopathy. The name Leigh’s syndrome goes back to the British psychiatrist and neuropathologist Archibald Denis Leigh. He first mentioned the disease in 1951, describing a six-year-old boy who suffered from developmental disorders that progressed rapidly. The boy died within six months. In his brain, there was evidence of capillary proliferation and extensive necrosis. Leigh’s disease usually sets in during infancy or early childhood. In contrast, adult-onset forms are very rare.
Causes
Leigh disease is caused by a disorder of mitochondrial metabolism. This affects the region for obtaining and providing energy. Various defects in the respiratory chain region complex I to IV are possible. The respiratory chain gains ATP (adenosine triphosate) as a supplier of energy by glycolysis. Furthermore, defects in the citric acid cycle can occur. Responsible for the defects are often deletions within the mtDNA. Sometimes complex II, biotinidase or mitochondrial ATPase are affected by point mutations. The changes within the mitochondrial genome occur through maternal inheritance. Thus, male sperm do not introduce their mtDNA into the zygote when fertilizing the female egg. Genes whose coding occurs in the nDNA are in most cases autosomal recessive. The frequency of mitochondriopathies ranges from 1 to 1.5 per 10,000, making Leigh syndrome one of the rare mitochondrial diseases. The hereditary disease occurs more frequently in boys than in girls. This circumstance can be traced back to mutations that are bound to the X chromosome. They occur more frequently in some families. If Leigh syndrome is already present in a family member, the frequency of the disease is 33 percent higher than in the case of autosomal recessive inheritance. There, the frequency is 25 percent.
Symptoms, complaints and signs
About 70 to 80 percent of all sufferers are affected by the classic form of Leigh syndrome. In them, the disease begins in infancy or toddlerhood, while in the run-up their development is normal. The first symptoms appear between 3 months and 2 years of age and can be gradual, subacute or acute. In about 75 percent, the symptoms are gradual. The symptoms that appear depend on which region of the brain is affected by the disease. Thus, there may be muscle weakness, muscle paresis, epileptic seizures, difficulty swallowing, vomiting, hypotonia and delayed development. Furthermore, there are eye symptoms such as paralysis of the eye muscles, nystagmus and breathing disorders. In about 37 percent of all affected children, there is also mental retardation. Due to the epileptic seizures, there is a risk of critical situations. About 55 percent of all children also suffer from loss of appetite and feeding problems. Another typical feature of the hereditary disease is retardation of physical growth. Also in the realm of possibility are cardiac disorders such as heart failure, deafness, kidney changes, hormonal disorders and sensory disturbances. It is not uncommon for severe complications to threaten the death of the child.
Diagnosis and course of the disease
Leigh syndrome can be diagnosed by its symptoms as well as a history of the child’s family. It is not uncommon for psychomotor developmental disorders to be present in Leigh syndrome. Other diagnostic options include determining neurological status by testing pathological reflexes, magnetic resonance imaging (MRI), and lumbar puncture, which involves examination of cerebrospinal fluid (CSF). To detect ragged red fibers, a muscle biopsy can be performed. As a rule, Leigh syndrome takes an unfavorable course. Affected children usually die after only a few years, mostly due to respiratory dysregulation. The prognosis is more favorable if a juvenile or adult form of the disease is present.In the future, the medical community hopes to halt the dangerous mitochondriopathy by using sirolimus, which would have a positive impact on survival.
Complications
Leigh syndrome leads to various complaints that significantly reduce and limit the quality of life of affected individuals. As a rule, patients are dependent on the help of other people in their daily lives because of the syndrome. Children in particular suffer from severe developmental delays. Patients suffer from severe muscle weakness and epileptic seizures. These can also be associated with pain. Furthermore, swallowing difficulties occur, so that the affected persons can no longer take in food and liquids in the usual way. The quality of life is considerably reduced as a result. There is also a loss of appetite and, furthermore, cardiac insufficiency, so that, in the worst case, patients can die of cardiac death. Unfortunately, a causal treatment of Leigh syndrome is not possible. Those affected are usually dependent throughout their lives on therapies that can make everyday life more bearable. It is not uncommon for parents to be dependent on psychological treatments as well, as they often suffer from depression and other psychological ailments. Leigh syndrome may also reduce the life expectancy of the affected person.
When should you see a doctor?
Because Leigh syndrome is a hereditary condition and does not cure itself, a doctor should always be consulted. Without treatment, Leigh syndrome can lead to the death of the affected person. A doctor should be consulted if the person with Leigh syndrome suffers from muscle weakness or general weakness. Likewise, epileptic seizures or difficulty swallowing may indicate the syndrome. Respiratory disorders or mental retardation may also be clues. If these complaints occur in childhood, a doctor should always be consulted. Furthermore, heart complaints or deafness also indicate Leigh syndrome. These can develop into serious complications that can lead to the death of the patient. An initial examination can be performed by a general practitioner or a pediatrician for Leigh syndrome. Further treatment depends on the exact symptoms and their severity.
Treatment and therapy
A causal treatment of Leigh syndrome could not be achieved so far. Thus, there are various therapeutic approaches, which include administering antioxidants or electron transporters, stimulating residual enzyme activity with cofactors such as vitamin B1 (thiamine), replenishing the energy storage pool, a ketogenic diet, reducing toxic metabolites, or supplementation for secondary deficiency. The manner in which mitochondrial metabolic dysfunction is treated ultimately depends on the particular diagnosis, which varies from individual to individual. This usually requires complex molecular genetic and biochemical analyses. The most promising options should therefore be carefully reviewed. If a pyruvate dehydrogenase defect is present, a ketogenic diet, which has a high fat content with only a few carbohydrates, is considered promising. Acidosis can be influenced by the use of sodium carbonate. Special drugs are administered for the therapy of seizures. However, some drugs such as valproate or tetracyclines are unfavorable and should be avoided. Other therapeutic measures such as occupational therapy, physiotherapy or speech therapy are available to alleviate the symptoms. In addition, medical science is researching other useful treatment measures.
Outlook and prognosis
Leigh syndrome has a relatively poor prognosis. The life expectancy of affected children is only a few years. With modern therapeutic methods, the symptoms can be alleviated, but the course of the disease cannot be slowed down. The exact prognosis depends on the severity of Leigh’s disease. The patient’s general condition is also an important factor. The physician will include all relevant information in his diagnosis and prognosis. Depending on whether and which complications occur, the prognosis may improve or worsen in the course of the disease.The physician in charge will usually not give a conclusive prognosis, but only a broad time frame. Leigh syndrome is a fatal disease, which is associated with considerable discomfort for the patients. This also affects the parents, who sometimes suffer severely from the child’s illness. After the death of the child, the parents should start a therapy to cope with the grief. Thus, there is no good life expectancy for the affected persons themselves. The relatives can get over the child’s illness with professional guidance, and in many cases the mothers can even become pregnant again.
Prevention
Leigh disease is one of the congenital hereditary diseases. For this reason, there are no useful preventive measures against the syndrome.
Follow-up
There are usually no special measures of aftercare available to the affected person for Leigh syndrome, since this disease is a hereditary disease, and in the process it cannot be completely cured. However, the affected person should consult a doctor at the first signs and symptoms of the disease, so that no further complications or complaints can occur, since this disease cannot be cured on its own. If there is a desire to have children, genetic testing and counseling can provide information about the likelihood of Leigh syndrome occurring in descendants. In most cases, the symptoms of Leigh syndrome can be relatively well alleviated by taking medications and various supplements. Here, the affected person should always pay attention to a regular intake and also a correct dosage of the medication. If there is any uncertainty, a doctor should be consulted first. A healthy lifestyle with a healthy and varied diet also has a positive effect on the course of the disease. Most of those affected also continue to rely on the measures of physiotherapy, although many of the exercises can also be carried out in the patient’s own home. As a rule, the syndrome does not reduce the life expectancy of the affected person.
What you can do yourself
In the absence of a specific treatment that could help cure the neurological condition, sufferers are still left with some self-help options. These can help to modestly mitigate the impairments to their daily lives caused by the severe physical as well as mental limitations. As some therapies have shown in individual cases, a change in diet to a particularly low-carbohydrate diet can reduce the concentration of lactic acid and the associated drop in blood pH. Against this background, mainly vegetables and dairy products should be on the daily menu to bring about a weakening of the symptoms and a slight improvement in the general state of health. Vitamin B1 (thiamine) and B2 (riboflavin) are also recommended. Highly sugary foods should be avoided. For those affected, occupational therapy also promises to alleviate their symptoms. The goal of treatment is to maintain maximum independence in everyday life. Since affected persons usually have communicative deficits in addition to physical limitations, a visit to a speech therapist can prove to be a valuable aid in everyday life. Here, possible articulation deficits and speech disorders are mitigated and compensated for in the best possible way through targeted training. In this way, people suffering from Leigh Syndrome can develop and secure their social participation in daily life to a greater extent. Taking advantage of physiotherapeutic services helps individuals improve their general ability to move and function.
