Leigh syndrome is a rare inherited neurometabolic disorder that affects the central nervous system. This disorder begins in infants between the ages of 3 months and 2 years. Rarely, it can occur in teenagers and adults.

Symptoms of Leigh syndrome usually progress rapidly, and may include:

• Poor sucking ability
• Loss of head control and motor skills
• Loss of appetite
• Vomiting
• Irritability
• Continuous crying
• Seizures

 As the disorder progresses, symptoms may also include:

• Generalized weakness
• Lack of muscle tone
• Episodes of lactic acidosis, which can lead to impairment of respiratory and kidney function

Leigh syndrome can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase.

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. These genetic mutations result in a chronic lack of energy in the cells which affects the central nervous system and causes progressive degeneration of motor functions.

There is also a form of Leigh syndrome (X-linked recessive inheritance) that is the result of mutations in a gene that produces another group of substances important for cell metabolism. This gene is only found on the X chromosome. 

The most common treatment for Leigh syndrome is thiamine or Vitamin B1. Oral sodium bicarbonate or sodium citrate may be prescribed to manage lactic acidosis. Researchers are testing dichloroacetate to establish its effectiveness in treating lactic acidosis. In individuals with the X-linked form of Leigh syndrome, a high-fat, low-carbohydrate diet may be recommended.

Leigh syndrome can be caused by mutations in any of more than 75 different genes. Most of our genes are made up of DNA in the cell's nucleus (nuclear DNA). Some of our genes are made up of DNA in other cell structures called mitochondria (mitochondrial DNA, or mtDNA). Most people with Leigh syndrome have a mutation in nuclear DNA, and about 20% have a mutation in mtDNA.

Most genes associated with Leigh syndrome are involved in the process of energy production in mitochondria (oxidative phosphorylation). Five protein complexes, named complex I through complex IV, are involved in this process. Many of the gene mutations associated with Leigh syndrome disrupt the function of proteins in these complexes, how the complexes form, or additional steps related to energy production. Researchers believe that impaired oxidative phosphorylation may cause cells to die because they don't have enough energy. The death of brain cells likely contributes to the neurologic features of the condition, while the death of cells in other tissues may lead to additional symptoms in other parts of the body.

• 25% chance to be affected
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier

• Each son has a 50% chance to be unaffected, and a 50% chance to be affected
• Each daughter has a 50% chance to be unaffected, and a 50% chance to be an unaffected carrier

• Developmental delay or regression
• Nystagmus
• Ophthalmoparesis (weakness in the muscles that control eye movement)
• Optic atrophy
• Ataxia
• Dysphagia
• Retinitis pigmentosa
• Deafness

• Distinct physical features
• Hormone abnormalities resulting in short stature or hypertrichosis
• Heart abnormalities (hypertrophic or dilated cardiomyopathy)
• Gastrointestinal symptoms such as diarrhea

Leigh syndrome may be diagnosed by using the following criteria, defined by Rahman et al. in 1996:

• Progressive neurologic disease with motor and intellectual developmental delay
• Signs and symptoms of brainstem and/or basal ganglia disease
• Raised lactate concentration in blood and/or cerebrospinal fluid (CSF)
• The presence of one or more of the following:
  • Characteristic features on brain imaging (CT scan or MRI)
  • Typical nervous system tissue changes
  • Typical nervous system tissue changes in a similarly affected sibling

After these criteria are met and a diagnosis of Leigh syndrome is made, molecular genetic testing can then differentiate between mtDNA-associated Leigh syndrome (caused by mutations in mtDNA) and nuclear gene-encoded Leigh syndrome (caused by mutations in nuclear DNA). A diagnosis of nuclear gene-encoded Leigh syndrome can be made either by identifying a mutation in nuclear DNA, or by excluding the presence of a mutation in mtDNA.

Because not all patients have increased lactate levels, recent studies proposed new diagnostic criteria excluding the raised lactate levels as a prerequisite. The remaining criteria are similar, but add mitochondrial dysfunction as a criterion.

A diagnosis of Leigh-like syndrome may be considered in individuals who do not meet the strict diagnostic criteria but have features resembling Leigh syndrome.