Leber hereditary optic neuropathy

What causes Leber hereditary optic neuropathy (LHON)?

Leber hereditary optic neuropathy is a condition related to changes in mitochondrial DNA. Mutations in the MT-ND1, MT- ND4, MT- ND4L, and MT- ND6 genes cause LHON. These genes are contained in mitochondrial DNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA).

The genes related to Leber hereditary optic neuropathy each provide instructions for making a protein involved in normal mitochondrial function. These proteins are part of a large enzyme complex in mitochondria that helps convert oxygen and simple sugars to energy. Mutations in any of the genes disrupt this process. It remains unclear how these genetic changes cause the death of cells in the optic nerve and lead to the specific features of Leber hereditary optic neuropathy. Please visit the Genetic Home Reference Web site to learn more about how mutations in these genes cause Leber hereditary optic neuropathy.

Last updated on 05-01-20

How is Leber hereditary optic neuropathy (LHON) inherited?

Leber hereditary optic neuropathy is an inherited condition that has a mitochondrial pattern of inheritance. The gene mutations that cause this condition are found in the mitochondrial DNA. Mitochondria are inherited from a person's mother, and as a result, only females pass mitochondrial conditions on to their children. Men can be affected, but they cannot pass the condition on to their children.

Often, people who develop the features of Leber hereditary optic neuropathy have no family history of the condition. Because a person may carry a mitochondrial DNA mutation without experiencing any signs or symptoms, it is hard to predict which members of a family who carry a mutation will eventually develop vision loss or other medical problems associated with Leber hereditary optic neuropathy. It is important to note that all females with a mitochondrial DNA mutation, even those who do not have any signs or symptoms, will pass the genetic change to their children.

Last updated on 05-01-20

What is Leber hereditary optic neuropathy (LHON)?

Leber hereditary optic neuropathy (LHON) is a condition characterized by vision loss. Vision loss is typically the only symptom of LHON. Some families with additional signs and symptoms have been reported and are said to have "LHON plus", a condition which includes vision loss, tremors, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). Some affected individuals develop features similar to multiple sclerosis. LHON is caused by mutations in the MT-ND1, MT- ND4, MT- ND4L, and MT- ND6 genes. LHON has a mitochondrial pattern of inheritance; however, there are many cases in which there are no other cases of LHON in the family. Treatment is supportive and may include visual aids. There is ongoing research for more effective treatment.

Last updated on 05-01-20

Are most people with Leber hereditary optic neuropathy (LHON) blind?

The severity of the vision loss experienced by people with Leber hereditary optic neuropathy varies. Visual acuity (sharpness) can range from 20/50 to no light perception, and depends on the nature of the gene mutation. Many people with this condition lose almost all of their central vision, and have profoundly affected color vision, but may have some remaining peripheral vision. Most of these individuals can be considered legally blind. Vision tends to be most severely impaired in people with the MT-ND4 gene mutation, followed in order of decreasing severity by those with MT-ND1 , MT-CYB , and MT-ND6. Also, patients who has an earlier age of onset (< 20 years), slow visual deterioration, and a relatively large optic disc seem to have a better prognosis.

Last updated on 05-01-20

Who can I contact to learn more about Leber hereditary optic neuropathy (LHON)?

For more information on this condition, contact The National Eye Institute (NEI), part of the National Institutes of Health (NIH).

National Eye Institute (NEI)
Information Office
31 Center Drive MSC 2510
Bethesda, MD 20892-2510
Telephone: 301-496-5248
E-mail: 2020@nei.nih.gov
Web site: http://www.nei.nih.gov/

Last updated on 05-01-20

Are there any support groups for people with Leber hereditary optic neuropathy (LHON)?

Yes. To view a list of organizations that provide support and additional information on Leber hereditary optic neuropathy, click here.

Last updated on 05-01-20

Will the vision loss associated with Leber hereditary optic neuropathy (LHON) improve with time?

Partial recovery of vision loss has been reported, but this is rare. When partial recovery does occur it tends to begin around 6 months to several years after disease onset. The chance of vision recovery appears to be higher with certain gene mutations, namely MT-ND6 (37% experience some recovery), MT- ND1 (22% experience some recovery), and the MT-CYB (28% experience some recovery). Please visit the following link from GeneReviews to learn more about visual recovery rates according to the specific mutation: Visual Recovery Rates by Pathogenic Variant in Individuals with LHON

Last updated on 05-01-20

Can certain foods or vitamins prevent vision loss in those with Leber hereditary optic neuropathy (LHON)? Can surgery be done to fix the vision loss?

There is no specific therapy or surgery to treat or prevent the specific vision loss due to Leber hereditary optic neuropathy. While vitamin supplements have been advocated, they have not been confirmed to be of value. Management of affected individuals is usually supportive, with provision of visual aids. Those with established LHON mitochondrial DNA mutations are advised not to smoke and to moderate their alcohol intake. People with Leber hereditary optic neuropathy may also find it helpful to speak with other affected individuals and to seek extra psychosocial or counseling support.

Small studies have reported a benefit from using quinone analogues, such as ubiquinone (Coenzyme Q10) and idebenone, during the acute phase of this condition, associated with vitamin C and vitamin B12. Targeted gene therapy is under exploration.High-dose oral idebenone should therefore be considered as a treatment option, especially for individuals with LHON with relatively recent disease onset. In an open-label study of five individuals with acute LHON treated within 90 days of disease onset, the antioxidant α-tocotrienol-quinone (EPI-743), a vitamin E derivative, showed good results.

Last updated on 05-01-20

What are the chances that a woman with Leber hereditary optic neuropathy (LHON) will pass the mutation on to her children?

Women with LHON who have a mitochondrial DNA gene mutation will always pass the mutation on to her children. However, more than 50 percent of males with a mutation and more than 85 percent of females with a mutation never experience vision loss or related medical problems. Additional factors may determine whether a person develops the signs and symptoms of this disorder. Environmental factors such as smoking and alcohol use may be involved, although studies have produced conflicting results. Researchers are also investigating whether changes in additional genes (nuclear DNA genes; Nuclear DNA is found within the nucleus of our cells), contribute to the development of signs and symptoms. As a result, is it very difficult to predict the likelihood a child will develop vision loss.

Last updated on 05-01-20

Is the vision loss due to Leber hereditary optic neuropathy (LHON) permanent?

Although central vision gradually improves in a small percentage of cases, in most cases the vision loss is profound and permanent. The vision loss often begins in young adults. However, the rate of vision loss varies considerably, from sudden severe vision loss within one day, to gradual vision loss over the course of months. Also, once the vision stabilizes, further vision changes appear to be rare.

Last updated on 05-01-20

Do all people with these gene mutations develop Leber hereditary optic neuropathy (LHON)?

No. Many people with a mutation that causes LHON do not develop any features of the disorder (more than 50% of males with a mutation and more than 85 % of females with a mutation never will have vision loss or other medical problems related to LHON). Additional factors, including the specific gene mutation that the person has, may determine whether a person develops the signs and symptoms of this disorder. Environmental factors such as smoking and alcohol use may also be involved, although studies of these factors are conflicting.

Last updated on 05-01-20

How might Leber hereditary optical neuropathy (LHON) be treated?

Currently, there is no cure for this disease but there are several ongoing studies aiming to find an effective treatment. Management of affected individuals is usually supportive, with provision of visual aids.

High-dose oral idebenone may be considered as a treatment option, especially for individuals with LHON with relatively recent disease onset. Some studies have reported a benefit from using idebenone with quinone analogues, such as ubiquinone (Coenzyme Q10) and with vitamin C and vitamin B12.

In an open-label study of five individuals with acute LHON treated within 90 days of disease onset, the antioxidant α-tocotrienol-quinone (EPI-743), a vitamin E derivative, showed good results.

Those with established LHON mitochondrial DNA mutations are advised not to smoke and to limit their alcohol intake. People with Leber hereditary optic neuropathy may also find it helpful to speak with other affected individuals and to seek extra psychosocial or counseling support.

Last updated on 05-01-20

Name: United Mitochondrial Disease Foundation 8085 Saltsburg Road, Suite 201
Pittsburgh, PA, 15239 , United States
Phone: +1-412-793-8077 Toll Free: 1-888-317-8633 Fax : +1-412-793-6477 Email: info@umdf.org Url: https://www.umdf.org
Name: The Mitochondria Research and Medicine Society PO Box 55322
Birmingham, AL,
Phone: 716-907-4349 Fax : 716-845-1047 Email: contact@mitoresearch.org Url: http://www.mitoresearch.org
Name: International Foundation for Optic Nerve Disease (IFOND) PO Box 777
Cornwall, NY, 12518 , United States
Phone: 6572067250 Email: ifond@aol.com Url: http://www.ifond.org
Name: Leber's Hereditary Optic Neuropathy Website Url: http://www.lhon.org

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