This is thought to be caused by a blockage in the enzyme thiamine-diphosphate kinase, and therefore treatment in some patients would be to take thiamine triphosphate daily.

[7] Infants with the syndrome have symptoms that include diarrhea, vomiting, and dysphagia (trouble swallowing or sucking), leading to a failure to thrive.

Hypertrophic cardiomyopathy (thickening of part of the heart muscle) is also sometimes found and can cause death;[1] asymmetric septal hypertrophy has also been associated with Leigh syndrome.

[9] In children with Leigh-syndrome associated ventricular septal defects, caused by pyruvate dehydrogenase deficiency, high forehead and large ears are seen; facial abnormalities are not typical of Leigh syndrome.

[1] Disorders of oxidative phosphorylation, the process by which cells produce their main energy source of adenosine triphosphate (ATP), may be caused by mutations in either mtDNA or in nuclear encoded genes.

This and other point mutations associated with Leigh syndrome destabilize or malform the protein complex and keep energy production down in affected cells.

[13] Some types of SURF1 mutations cause a subtype of Leigh syndrome that has a particularly late onset but similarly variable clinical course.

[15] Patients with the neurologic presentation are hypotonic (low muscle tone), feed poorly, lethargic, and develop seizures, mental retardation, microcephaly, blindness and spasticity secondary to contractures.

[15] "Between these two extremes, there is a continuous spectrum of intermediate forms...A number of patients with primarily neurological symptoms fit into the category of Leigh's syndrome.

[1] The type of Leigh syndrome found at a much higher rate in the Saguenay–Lac-Saint-Jean region of Quebec is caused by a mutation in the LRPPRC gene, located on the small ('p') arm of chromosome 2.

This subtype of the disease was first described in 1993 in 34 children from the region, all of whom had a severe deficiency in cytochrome c oxidase (COX), the fourth complex in the mitochondrial electron transport chain.

Children with the disease are developmentally delayed, have mildly dysmorphic facial features, including hypoplasia of the midface and wide nasal bridge, chronic metabolic acidosis, and hypotonia (decreased muscular strength).

Other symptoms include tachypnea (unusually quick breathing rate), poor sucking ability, hypoglycemia (low blood sugar), and tremors.

[16] The characteristic symptoms of Leigh syndrome are at least partially caused by bilateral, focal lesions in the brainstem, basal ganglia, cerebellum, and other regions of the brain.

The brain stem is involved in maintaining basic life functions such as breathing, swallowing, and circulation; the basal ganglia and cerebellum control movement and balance.

[1] The lactic acidosis sometimes associated with Leigh syndrome is caused by the buildup of pyruvate, which is unable to be processed in individuals with certain types of oxidative phosphorylation deficiencies.

[7] Dystonia, nystagmus, and problems with the autonomic nervous system suggest damage to the basal ganglia and brain stem potentially caused by Leigh syndrome.

Laboratory findings of lactic acidosis or acidemia and hyperalaninemia (elevated levels of alanine in the blood) can also suggest Leigh syndrome.

Perinatal asphyxia can cause bilateral ganglial lesions and damage to the thalamus, which are similar to the signs seen with Leigh syndrome.

When hyperbilirubinemia is not treated with phototherapy, the bilirubin can accumulate in the basal ganglia and cause lesions similar to those seen in Leigh syndrome.

[19] In 2016, John Zhang and his team at New Hope Fertility Center in New York, USA, performed a spindle transfer mitochondrial donation technique on a mother in Mexico who was at risk of producing a baby with Leigh disease.

[9] In 1968, the disease's link with mitochondrial activity was first ascertained, though the mutations in cytochrome c oxidase and other electron transport chain proteins were not discovered until 1977.