National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Mitochondrial DNA-associated Leigh syndrome


Other Names:
MILS; Leigh disease, maternally inherited; Subacute necrotizing encephalomyelopathy maternally inherited; MILS; Leigh disease, maternally inherited; Subacute necrotizing encephalomyelopathy maternally inherited; Maternally inherited Leigh syndrome See More
Categories:
This disease is grouped under:
Mitochondrial DNA-associated Leigh syndrome is a progressive brain disorder that usually appears in infancy or early childhood.[1] Affected children may experience vomiting, seizures, delayed development, muscle weakness, and problems with movement. Heart disease, kidney problems, and difficulty breathing can also occur in people with this disorder. Mitochondrial DNA-associated Leigh syndrome is a subtype of Leigh syndrome and is caused by changes in mitochondrial DNA. Mutations in at least 11 mitochondrial genes have been found to cause mtDNA-associated Leigh syndrome.[2] This condition has an inheritance pattern known as maternal or mitochondrial inheritance.[2][3] Because mitochondria can be passed from one generation to the next only through egg cells (not through sperm cells), only females pass mitochondrial DNA-associated Leigh syndrome to their children.
Last updated: 1/27/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of Krebs cycle metabolism 0000816
Increased CSF lactate 0002490
30%-79% of people have these symptoms
Bilateral tonic-clonic seizure
Grand mal seizures
0002069
Chorea 0002072
Dyskinesia
Disorder of involuntary muscle movements
0100660
Dystonia 0001332
Episodic vomiting 0002572
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Focal T2 hyperintense basal ganglia lesion 0007183
Gait ataxia
Inability to coordinate movements when walking
0002066
Generalized myoclonic seizure 0002123
Increased serum lactate 0002151
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Lacticaciduria
High urine lactic acid levels
0003648
Muscle weakness
Muscular weakness
0001324
Ophthalmoparesis
Weakness of muscles controlling eye movement
0000597
Pigmentary retinopathy 0000580
Sensorimotor neuropathy
Nerve damage causing decreased feeling and movement
0007141
Severe global developmental delay 0011344
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
5%-29% of people have these symptoms
Abnormal renal tubule morphology 0000091
Abnormal speech prosody 0031434
Apnea 0002104
Bulbar signs 0002483
Cardiac conduction abnormality 0031546
Demyelinating peripheral neuropathy 0007108
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood
[ more ] 		0002376
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty
[ more ] 		0002015
Episodic respiratory distress
Episodic difficulty breathing
0004885
Fever 0001945
Hepatic failure
Liver failure
0001399
Hepatomegaly
Enlarged liver
0002240
Hyperalaninemia
Increased blood alanine
Increased serum alanine
[ more ] 		0003348
Hyperreflexia
Increased reflexes
0001347
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Hyperventilation
Rapid breathing
0002883
Hyporeflexia
Decreased reflex response
Decreased reflexes
[ more ] 		0001265
Hypothermia
Abnormally low body temperature
0002045
Infantile spasms 0012469
Mitochondrial myopathy 0003737
Multiple glomerular cysts 0100611
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy 0000648
Rod-cone dystrophy 0000510
Segmental peripheral demyelination/remyelination 0003481
Sensorineural hearing impairment 0000407
1%-4% of people have these symptoms
Low plasma citrulline 0003572
Ragged-red muscle fibers 0003200
Percent of people who have these symptoms is not available through HPO
Abnormal pattern of respiration
Abnormal respiratory patterns
Unusual breathing patterns
[ more ] 		0002793
Ataxia 0001251
Autosomal recessive inheritance 0000007
CNS demyelination 0007305
Dysarthria
Difficulty articulating speech
0001260
Emotional lability
Emotional instability
0000712
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Global developmental delay 0001263
Hepatocellular necrosis
Death of liver cells
0001404
Hypertrichosis 0000998
Infantile onset
Onset in first year of life
Onset in infancy
[ more ] 		0003593
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Lactic acidosis
Increased lactate in body
0003128
Mitochondrial inheritance 0001427
Muscular hypotonia
Low or weak muscle tone
0001252
Ophthalmoplegia
Eye muscle paralysis
0000602
Progressive
Worsens with time
0003676
Psychomotor retardation 0025356
Ptosis
Drooping upper eyelid
0000508
Respiratory failure 0002878
Respiratory insufficiency
Respiratory impairment
0002093
Seizure 0001250
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.
Leigh syndrome in general is rare and is estimated to affect about 1 in 30,000 to 1 in 40,000 people at birth. Mitochondrial DNA-associated Leigh syndrome, which is more rare than nuclear gene-encoded Leigh syndrome, is likely to occur in about 1 in 100,000 to 1 in 140,000 births.[4]

Leigh syndrome is much more common in certain populations. For example, it occurs in approximately 1 in 2,000 newborns in the Saguenay Lac-Saint-Jean region of Quebec, Canada and in approximately 1 in 1,700 on the Faroe Islands (between Norway and Iceland).[5]
Last updated: 12/27/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 
  • The North American Mitochondrial Disease Consortium (NAMDC) is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research.

Patient Registry

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • The Neuromuscular Disease Center at Washington University provides information about Leigh syndrome.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Mitochondrial DNA-associated Leigh syndrome. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • How is neuropathy ataxia retinitis pigmentosa (NARP) related to maternally inherited Leigh syndrome (MILS)? See answer


  1. MT-ATP6. Genetics Home Reference. October 2011; http://ghr.nlm.nih.gov/gene/MT-ATP6.
  2. Thornburn DR, Rahman SR. Mitochondrial DNA-Associated Leigh Syndrome and NARP. GeneReviews. April 17, 2014; http://www.ncbi.nlm.nih.gov/books/NBK1173/.
  3. Neuropathy, ataxia, and retinitis pigmentosa. Genetics Home Reference. November 2006; http://ghr.nlm.nih.gov/condition/neuropathy-ataxia-and-retinitis-pigmentosa.
  4. Thronburn DR & Rahman S.. Mitochondrial DNA-Associated Leigh Syndrome and NARP. GeneReviews. April 17, 2014; http://www.ncbi.nlm.nih.gov/books/NBK1173/.
  5. Leigh syndrome. Genetics Home Reference. June, 2016; https://ghr.nlm.nih.gov/condition/leigh-syndrome.