Mitochondrial DNA-associated Leigh syndrome

Title

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:

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders; Congenital and Genetic Diseases; Eye diseases; Metabolic disorders; Nervous System Diseases; RDCRN See More

This disease is grouped under:

Leigh syndrome

Summary Summary

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

Symptoms Symptoms

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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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 7/1/2020

Diagnosis Diagnosis

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.

Statistics Statistics

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

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.
You can submit a question to Ask the Mito Doc, a service of the United Mitochondrial Diseases Foundation. Information contained in Ask the Mito Doc^SM is for informational and educational purposes only.

Research Research

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

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Mitochondrial DNA-associated Leigh syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for Mitochondrial DNA-associated Leigh syndrome:
North American Mitochondrial Disease Consortium (NAMDC) Contact Registry
Mitochondrial Disease Community Registry
People Against Leigh Syndrome Registry

Organizations Organizations

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

MitoAction
PO Box 51474
Boston, MA 02205
Toll-free: 1-888-648-6228
Telephone: 1-888-MITO-411 (648-6411) for support line
E-mail: info@mitoaction.org
Website: https://www.mitoaction.org/
People Against Leigh Syndrome (PALS)
Lori Martin, Director
Houston, TX,
Telephone: 713-863-0485
E-mail: director@peopleagainstleighs.org
Website: http://peopleagainstleighs.org/
The Mitochondria Research and Medicine Society
PO Box 55322
BLSC Building, Room # 3-316
Elm and Carlton Streets
Birmingham, AL
Telephone: 716-907-4349
Fax: 716-845-1047
E-mail: contact@mitoresearch.org
Website: http://www.mitoresearch.org
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 1-888-317-8633
Telephone: +1-412-793-8077
Fax: +1-412-793-6477
E-mail: info@umdf.org
Website: https://www.umdf.org

Do you know of an organization? We want to hear from you.

Learn More Learn More

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

Huntsman RJ, Sinclair DB, Bhargava R, Chan A. Atypical presentations of Leigh syndrome: A case series and review. Pediatr Neurol 2005;32:334-340.

News & Events News & Events

News

NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

GARD Answers GARD Answers

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

Have a question? Contact a GARD Information Specialist.

References References

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