- Subacute necrotizing encephalopathy
- Necrotizing encephalopathy infantile subacute of Leigh
- Leigh's necrotizing encephalopathy
Your QuestionI'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.
We have identified the following information that we hope you find helpful. If you still have questions, please contact us.
Questions on this page
- What is Leigh syndrome?
- What are the signs and symptoms of Leigh syndrome?
- What is known about Leigh syndrome diagnosed in adolescence or adulthood?
- What causes Leigh syndrome?
- How is Leigh syndrome inherited?
- How is Leigh syndrome diagnosed?
- What tests are considered when diagnosing Leigh syndrome?
- Is there genetic testing available for the mitochondrial and nuclear genes known to cause Leigh syndrome?
- How can I find a genetics professional in my area?
- What treatment is available for Leigh syndrome?
- Mitochondrial DNA-associated Leigh syndrome follows a mitochondrial inheritance pattern (also called maternal inheritance)
- Nuclear gene-encoded Leigh syndrome may be inherited in an autosomal recessive or X-linked manner, depending on the responsible gene.
Central nervous system abnormalities
- Developmental delay or regression
- Ophthalmoparesis (weakness in the muscles that control eye movement)
- Optic atrophy
- Dysphagia resulting in feeding difficulties, paralysis of cranial nerves, weakness, hypotonia, dystonia, or breathing abnormalities
- Retinitis pigmentosa
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:
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.
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.
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).
- 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 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.
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.
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.
The following online resources can help you find a genetics professional in your community:
- The National Society of Genetic Counselors provides a searchable directory of US and international genetic counseling services.
- The American College of Medical Genetics has a searchable database of US genetics clinics.
- The University of Kansas Medical Center provides a list of US and international genetic centers, clinics, and departments.
- The American Society of Human Genetics maintains a database of its members, which includes individuals who live outside of the United States. Visit the link to obtain a list of the geneticists in your country, some of whom may be researchers that do not provide medical care.
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).
Other treatment may be symptomatic. For instance, sodium bicarbonate or sodium citrate may be prescribed to manage lactic acidosis or antiepileptic medication for seizures.
- Leigh's Disease Information Page. National Institute of Neurological Disorders and Stroke. December, 2011; http://www.ninds.nih.gov/disorders/leighsdisease/leighsdisease.htm.
- Thornburn DR, Rahman SR. Mitochondrial DNA-Associated Leigh Syndrome and NARP. GeneReviews. April 17, 2014; http://www.ncbi.nlm.nih.gov/books/NBK1173/.
- Leigh syndrome. Genetics Home Reference. October, 2011; http://ghr.nlm.nih.gov/condition/leigh-syndrome.
- Rahman S & Thorburn D. Nuclear Gene-Encoded Leigh Syndrome Overview. GeneReviews. October 1, 2015; http://www.ncbi.nlm.nih.gov/books/NBK320989/.
- Finsterer J. Leigh and Leigh-Like Syndrome in Children and Adults. Pediatr Neurol. 2008;
- Thronburn DR & Rahman S.. Mitochondrial DNA-Associated Leigh Syndrome and NARP. GeneReviews. April 17, 2014; http://www.ncbi.nlm.nih.gov/books/NBK1173/.
- Leigh's disease. National Organization for Rare Disorders (NORD). 2009; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/392/viewAbstract. Accessed 10/6/2011.