Rare Cardiology News

Disease Profile

Mitochondrial DNA-associated Leigh syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Childhood

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ICD-10

E88.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

MILS; Leigh disease, maternally inherited; Subacute necrotizing encephalomyelopathy maternally inherited;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

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 DNAMutations 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.

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.

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.

    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

      Organizations Providing General Support

        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

              References

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

              Rare Cardiology News

              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
              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
              Ophthalmoplegia
              Eye muscle paralysis
              0000602