Leigh’s disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years. Rarely, it occurs in teenagers and adults.
Leigh’s disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase. Symptoms of Leigh’s disease usually progress rapidly. The earliest signs may be poor sucking ability,and the loss of head control and motor skills.
These symptoms may be accompanied by loss of appetite, vomiting, irritability, continuous crying, and seizures. As the disorder progresses, symptoms may also include generalized weakness, lack of muscle tone, and episodes of lactic acidosis, which can lead to impairment of respiratory and kidney function.
In Leigh’s disease, genetic mutations in mitochondrial DNA interfere with the energy sources that run cells in an area of the brain that plays a role in motor movements. The primary function of mitochondria is to convert the energy in glucose and fatty acids into a substance called adenosine triphosphate (ATP).
The energy in ATP drives virtually all of a cell’s metabolic functions. Genetic mutations in mitochondrial DNA, therefore, result in a chronic lack of energy in these cells, which in turn affects the central nervous system and causes progressive degeneration of motor functions.
There is also a form of Leigh’s disease (called X-linked Leigh’s disease) which is the result of mutations in a gene that produces another group of substances that are important for cell metabolism. This gene is only found on the X chromosome.
Cause of Leigh’s Disease
There may be a number of different types of genetically determined enzyme defects which may cause Leigh’s disease. The majority of people with the disease experience defects of mitochondrial energy production, such as deficiencies of an enzyme of the mitochondrial respiratory chain complex, or the pyruvate dehydrogenase complex.
Most of the time, Leigh’s disease is inherited as an autosomal recessive trait. Mitochondrial inheritance and X-linked recessive Leigh’s disease are exceptions.
Is there any treatment?
The most common treatment for Leigh’s disease is thiamine or Vitamin B1. Oral sodium bicarbonate or sodium citrate may also be prescribed to manage lactic acidosis. Researchers are currently testing dichloroacetate to establish its effectiveness in treating lactic acidosis.
In individuals who have the X-linked form of Leigh’s disease, a high-fat, low-carbohydrate diet may be recommended.
Medical science has not discovered a treatment that is effective in slowing the progression of Leigh’s disease at this time. Doctors commonly administer Thiamine or vitamin B1. Sodium bicarbonate can also be prescribed to help manage lactic acidosis.
Researchers are testing dichloroacetate in an attempt to establish its effectiveness in the treatment of lactic acidosis. For people with X-linked Leigh’s disease, a high-fat, low-carbohydrate diet is recommended.
Due to the fact that there is no cure for Leigh’s disease, as well as the progressive nature of it, maintenance of the person’s functioning for as long as possible is the main focus instead of recovery.
Physical therapists many times help with exercises that can assist the person to maintain strength and range of motion. As Leigh’s disease progresses, an occupational therapist can provide the person with positioning devices for their comfort.
What is the prognosis?
The prognosis for individuals with Leigh’s disease is poor. Individuals who lack mitochondrial complex IV activity and those with pyruvate dehydrogenase deficiency tend to have the worst prognosis and die within a few years.
Those with partial deficiencies have a better prognosis, and may live to be 6 or 7 years of age. Some have survived to their mid-teenage years.
What research is being done?
The NINDS supports and encourages a broad range of basic and clinical research on neurogenetic disorders such as Leigh’s disease. The goal of this research is to understand what causes these disorders and then to apply these findings to new ways to diagnose, treat, and prevent them.
Diagnosing Leigh’s Disease
A diagnosis of Leigh’s disease is generally difficult because of the broad variability in clinical symptoms, as well as the variety of different genetic explanations that cause the disease. Genetic testing for specific nuclear or mitochondrial DNA mutation is something that can be helpful.
Laboratory studies can also help in achieving a diagnosis of Leigh’s disease. A Muscle biopsy can help to determine if the person is experiencing an abnormality associated with their mitochondria.
Because the mitochondria are responsible for the production of energy, if the person is experiencing a deficiency in a protein complex that plays an important function it may be detectable.
With Leigh’s disease, the deficiency can be found in one of five complexes which make up the mitochondrial respiratory system. Complex IV, referred to as, ‘Cytochrome C oxidase (COX),’ is one that people with the disease are commonly deficient in.
Unfortunately, while COX deficiency is associated with Leigh disease, it may also indicate other mitochondrial abnormalities. There are mutations found in additional complexes that may cause Leigh’s disease.