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Diseases

Genetic and Rare Diseases Information Center (GARD)

Leigh syndrome


Other Names for this Disease
  • LS
  • Subacute necrotizing encephalopathy
  • SNE
  • Necrotizing encephalopathy infantile subacute of Leigh
  • Leigh's necrotizing encephalopathy
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

I'd like to know as much as possible about Leigh syndrome. Could you also tell me what type of testing is available for the condition? I am particularly interested in learning more about genetic testing for the syndrome.

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is Leigh syndrome?

Leigh syndrome is a rare, inherited neurodegenerative condition. It usually begins in infancy, often after a viral infection. Rarely, it begins in the teenage or adult years. Signs and symptoms usually progress rapidly and may get worse after a viral infection. Early signs may include poor sucking ability; loss of head control and motor skills; loss of appetite; vomiting; and seizures.[1] As the disorder progresses, symptoms may include weakness and lack of muscle tone; spasticity; movement disorders; cerebellar ataxia; and peripheral neuropathy. Complications can lead impairment of respiratory, heart and kidney function. Leigh syndrome may be caused by changes (mutations) in either mitochondrial DNA or nuclear DNA:[2][3][4]
Some people with features very similar to those of Leigh syndrome are said to have "Leigh-like syndrome."[3] Treatment is generally supportive and focuses on the symptoms present.[3][4]
Last updated: 2/29/2016

What are the signs and symptoms of Leigh syndrome?

The symptoms of Leigh syndrome vary greatly from person to person. Although cases of individuals with Leigh syndrome with near normal neurologic findings have been documented, these cases are very rare. Most patients present with central nervous system and peripheral nervous system abnormalities, without involvement of other tissues.[5] The following neurological findings may be present in patients with Leigh syndrome:[1][5]

Central nervous system abnormalities

Peripheral nervous system abnormalities

Although Leigh syndrome usually only causes neurological abnormalities, there are individuals who present with non-neurologic abnormalities in addition to neurological abnormalities. There are also some patients who have abnormalities in other organs and few neurological abnormalities. The list below includes some of the non-neurologic abnormalities present in some individuals who have Leigh syndrome:[5]

Last updated: 3/3/2016

What is known about Leigh syndrome diagnosed in adolescence or adulthood?

A very small number of individuals with Leigh syndrome live beyond 10 years of age. Leigh syndrome in adolescents or adults may occur in patients who have Leigh syndrome who survive into adulthood, or in patients with a late onset of symptoms, or in patients who experience spontaneous recovery. Adults with Leigh syndrome usually have no neurological abnormalities, or with typical features of Leigh syndrome or mitochondrial disorders.[5]
Last updated: 12/10/2008

What causes Leigh syndrome?

Leigh syndrome can be caused by mutations in mitochondrial DNA (mtDNA) or in nuclear DNA. It is estimated that the majority of cases are caused by a mutation in nuclear DNA and that anywhere between 10%-40% of cases of Leigh syndrome are caused by a mutation in mtDNA.[6] In the majority of cases, dysfunction of the respiratory chain (particularly complexes I, II, IV, or V) of coenzyme Q or of the pyruvate dehydrogenase complex are responsible for the disease.

Mutations in the mitochondrial genes MT-ATP6 (most common) MT-TL1, MT-TK, MT-TW, MT-TV, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND5, MT-ND6, and MT-CO3 cause the mtDNA-associated Leigh syndrome.

Nuclear gene-encoded Leigh syndrome can be subdivided by the mode of inheritance and disease-causing gene. While pathogenic variants in more than 50 nuclear genes can cause nuclear gene-encoded Leigh syndrome, all but a few of these gene defects are associated with a very limited number of cases. Learn more about the genes associated with autosomal recessive Leigh syndrome, autosomal recessive Leigh-like syndrome and X-linked Leigh syndrome.

To obtain a listing of the various mutations associated with Leigh syndrome, visit the Online Mendelian Inheritance in Man (OMIM) Web page on Leigh syndrome or view the Leigh syndrome information page created by the Neuromuscular Disease Center at Washington University.  
Last updated: 3/3/2016

How is Leigh syndrome inherited?

The inheritance pattern for Leigh syndrome varies depending on the specific mutation causing the disease in the individual. These mutations can be inherited as an autosomal recessive trait, an X-linked recessive trait, or as a mutation found within the mitochondrial DNA. In some cases of Leigh syndrome, no genetic cause can be identified.[7]

The autosomal recessive form of Leigh syndrome has been linked to mutations in one of several different genes. These genes cause specific enzyme deficiencies. All of these different genetic defects seem to have a common effect on the central nervous system, resulting in progressive neurological deterioration.[7] 

In some cases, Leigh syndrome may be inherited from the mother as a mutation found within the mitochondrial DNA (mtDNA). Mitochondria regulate the production of cellular energy and carry the genetic blueprints for this process within their own unique DNA. All human mtDNA comes from the mother. An affected mother will pass the disease to all of her children (sons and daughters), but only the daughters will pass the mutation(s) to the next generation. These cases are sometimes referred to as maternally inherited Leigh syndrome (MILS).[7]
Last updated: 3/3/2016

How is Leigh syndrome diagnosed?

Rahman et al (1996) defined the following stringent diagnostic criteria for Leigh syndrome[6]:
  • 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)
  • One or more of the following:
    • Characteristic features of Leigh syndrome on neuroradioimaging (i.e., bilateral symmetric hypodensities [low density areas] in the basal ganglia on CT scan or bilateral symmetrical hyperintense [strong] signal abnormality in the brainstem and/or basal ganglia on T2-weighted MRI)
    • Typical neuropathologic changes: multiple focal symmetric lesions in the basal ganglia, thalamus, brainstem, dentate nuclei, and optic nerves (click here to learn about the different parts of the nervous system that might be affected)
    • Typical neuropathology in a similarly affected sibling
The diagnosis of mtDNA-associated Leigh syndrome is established using the above criteria and molecular genetic testing.[6]

The diagnosis of nuclear gene-encoded Leigh syndrome is also established using the above criteria and molecular genetic testing with either the  identification of the mutations in a specific nuclear gene or exclusion of mutation of mtDNA.[4] 

The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional. Please see a list of laboratories offering the genetic test for Leigh syndrome.
Last updated: 3/3/2016

What tests are considered when diagnosing Leigh syndrome?

Tests that may be useful in diagnosing Leigh syndrome include, measuring lactic acid concentration in body fluids (i.e., blood, urine, and/or cerebrospinal fluid, the fluid that surrounds the brain and spinal cord), brain imaging, muscle biopsy, respiratory chain enzyme studies, and genetic testing. To learn more about the various tests run for diagnosing Leigh syndrome, visit GeneReviews and scroll down to the "Testing" section.[6]
Last updated: 3/3/2016

Is there genetic testing available for the mitochondrial and nuclear genes known to cause Leigh syndrome?

Although genetic testing is not available for all genes associated with Leigh syndrome, there is genetic testing available for both mitochondrial genes and nuclear genes associated with the condition.

Please see a list of laboratories offering the genetic test for Leigh syndrome by visiting Genetic Testing Registry (GTR), a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional. 
Last updated: 3/3/2016

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 6/5/2014

What treatment is available for Leigh syndrome?

No treatment has proven effective for all individuals with Leigh syndrome.

However, some types of nuclear gene-encoded Leigh-like syndrome are treatable including: 
  • Biotin-thiamine-responsive basal ganglia disease (BTBGD) (also known as thiamine transporter-2 deficiency) (mutation of SLC19A3) 
  • Biotinidase deficiency (BTD) 
  • Coenzyme Q10 biosynthesis defect (PDSS2).
Nuclear gene-encoded Leigh-like syndrome should be rapidly tested biochemically or genetically as indicated or, if this is not possible, trials of the relevant vitamins/cofactors should be done as soon as the diagnosis is considered. If a person is diagnosed with one of these syndromes, the treatment may be continued for life. Treatment may include high doses of thiamine, coenzyme-Q, or L-carnitine. Some studies have shown that patients with Leigh syndrome due to a deficiency in coenzyme Q may benefit the most from treatment with coenzyme-Q, resulting in almost complete recovery or significant improvement of neurological abnormalities.[5]

Other treatment may be symptomatic. For instance, sodium bicarbonate or sodium citrate may be prescribed to manage lactic acidosis or antiepileptic medication for seizures.[1]
Last updated: 3/10/2016

References
Other Names for this Disease
  • LS
  • Subacute necrotizing encephalopathy
  • SNE
  • Necrotizing encephalopathy infantile subacute of Leigh
  • Leigh's necrotizing encephalopathy
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.