Description

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. 

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.

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.

Research

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. A registry for individuals with Leigh syndrome has been established at the University of Texas Health Science Center in Houston to collect valuable information about the medical status of patients and to increase understanding of how the disease progresses. The registry will also serve as a resource to researchers conducting clinical trials, speeding up the process of finding potential study subjects. To enroll, see https://peopleagainstleighs.org/registry/.   Information from the National Library of Medicine’s MedlinePlusDegenerative Nerve Diseases

MitoAction

Works to improve quality of life for adults and children affected by mitochondrial disease and to raise awareness about mitochondrial disorders and their relationship to other diseases.

United Mitochondrial Disease Foundation

Promotes research for cures and treatments of mitochondrial disorders and provides support for affected families. Represents adults and children alike and continues to serve families with a variety of programs.