Rare Nephrology News

Disease Profile

Mitochondrial genetic disorders

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

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ICD-10

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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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Categories

Congenital and Genetic Diseases

Summary

Mitochondrial genetic disorders refer to a group of conditions that affect the mitochondria (the structures in each cell of the body that are responsible for making energy). People with these conditions can present at any age with almost any affected body system; however, the brain, muscles, heart, liver, nerves, eyes, ears and kidneys are the organs and tissues most commonly affected. Symptom severity can also vary widely.[1][2] 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. Those caused by mutations in mitochondrial DNA are transmitted by maternal inheritance, while those caused by mutations in nuclear DNA may follow an autosomal dominant, autosomal recessive, or X-linked pattern of inheritance.[1][3] Treatment varies based on the specific type of condition and the signs and symptoms present in each person.[1][4]

Symptoms

People with mitochondrial genetic disorders can present at any age with almost any affected body system. While some conditions may only affect a single organ, many involve multiple organ systems including the brain, muscles, heart, liver, nerves, eyes, ears and/or kidneys. Symptom severity can also vary widely. The most common signs and symptoms include:[1][2]

  • Poor growth
  • Loss of muscle coordination
  • Muscle weakness
  • Seizures
  • Autism
  • Problems with vision and/or hearing
  • Developmental delay
  • Learning disabilities
  • Heart, liver, and/or kidney disease
  • Gastrointestinal disorders
  • Diabetes
  • Increased risk of infection
  • Thyroid and/or adrenal abnormalities
  • Autonomic dysfunction
  • Dementia

The United Mitochondrial Disease Foundation's website features a comprehensive list of possible symptoms (click here to see this information) and symptoms categorized by type of mitochondrial genetic disorder (click here to access this page).

Cause

Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria. Most DNA (hereditary material that is passed from parent to child) is packaged within the nucleus of each cell (known as nuclear DNA). However, mitochondria (the structures in each cell that produce energy) contain a small amount of their own DNA, which is known as mitochondrial DNA.[1][2]

When the mitochondria are not working properly, the body does not have enough energy to carry out its normal functions. This can lead to the variety of health problems associated with mitochondrial genetic disorders.[1][2]

Diagnosis

Unfortunately, mitochondrial genetic disorders can be difficult to diagnose, and many affected people may never receive a specific diagnosis. They are often suspected in people who have a condition that effects multiple, unrelated systems of the body. In some cases, the pattern of symptoms may be suggestive of a specific mitochondrial condition. If the disease-causing gene(s) associated with the particular condition is known, the diagnosis can then be confirmed with genetic testing.[1][5]

If a mitochondrial genetic disorder is suspected but the signs and symptoms do not suggest a specific diagnosis, a more extensive work-up may be required. In these cases, a physician may start by evaluating the levels of certain substances in a sample of blood or cerebrospinal fluid. Other tests that can support a diagnosis include:[1]

When possible, confirming a diagnosis with genetic testing can have important implications for family members. Identifying the disease-causing gene(s) will give the family information about the inheritance pattern and the risk to other family members. It will also allow other at-risk family members to undergo genetic testing.[1]

For more information regarding the diagnosis of mitochondrial genetic disorders, please visit the United Mitochondrial Disease Foundation's "Getting a Diagnosis" Web page.

GeneReviews also provides information on establishing a diagnosis of a mitochondrial disorder. Click on the link to view the article on this topic.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. 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.

    Treatment

    Treatment for mitochondrial genetic disorders varies significantly based on the specific type of condition and the signs and symptoms present in each person. The primary aim of treatment is to alleviate symptoms and slow the progression of the condition. For example, a variety of vitamins and other supplements have been used to treat people affected by mitochondrial conditions with varying degrees of success. Other examples of possible interventions include medications to treat diabetes mellitus, surgery for cataracts, and cochlear implantation for hearing loss.[4][1]

    For more general information about the treatment of mitochondrial genetic disorders, please visit GeneReviews.

    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 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

      • MitoAction provides information on this condition for patients and caregivers.
      • The Cleveland Clinic Web site has an information page on Mitochondrial genetic disorders. Click on the Cleveland Clinic link to view this page.
      • The United Mitochondrial Disease Foundation has an information page on Mitochondrial genetic disorders.

        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.
        • MitoAction provides information on this condition for health care professionals.
        • Nature Education’s Scitable provides a comprehensive explanation of mitochondrial DNA and the conditions that can be associated with mitochondrial DNA mutations.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Mitochondrial genetic disorders. Click on the link to view a sample search on this topic.

          References

          1. Patrick F Chinnery, PhD, FRCPath, FRCP, FMedSci. Mitochondrial Disorders Overview. GeneReviews. August 2014; https://www.ncbi.nlm.nih.gov/books/NBK1224/.
          2. About Mitochondrial Disease Mito FAQ. MitoAction. https://www.mitoaction.org/mito-faq. Accessed 1/26/2015.
          3. Vento JM, Pappa B. Genetic counseling in mitochondrial disease. Neurotherapeutics. April 2013; 10(2):243-250. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625385/.
          4. Treatments & Therapies. United Mitochondrial Disease Foundation. https://www.umdf.org/site/c.otJVJ7MMIqE/b.5692887/k.6686/Treatments__Therapies.htm. Accessed 4/3/2011.
          5. Getting a Diagnosis. United Mitochondrial Disease Foundation. https://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=7934633. Accessed 1/26/2015.

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