MT-ATP6 mitochondrially encoded ATP synthase 6

Neuropathy, ataxia, and retinitis pigmentosa

Also known as: NARP, NARP syndrome, Neurogenic muscle weakness, ataxia, and retinitis pigmentosa, Neuropathy, ataxia, and retinitis pigmentos.

What is Neuropathy, ataxia, and retinitis pigmentosa?

Neuropathy, ataxia, and retinitis pigmentosa (NARP) is a condition that causes a variety of signs and symptoms that mainly affect the nervous system. The condition typically begins in childhood or early adulthood, and the signs and symptoms usually worsen over time. Most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have vision loss caused by changes in the light-sensitive tissue that lines the back of the eye (the retina). In some cases, the vision loss results from a condition called retinitis pigmentosa. This eye disease causes the light-sensing cells of the retina gradually to deteriorate.

Learning disabilities and developmental delays are often seen in children with NARP, and older individuals with this condition may experience a loss of intellectual function (dementia). Other features of NARP include seizures, hearing loss, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). These signs and symptoms vary among affected individuals.

Source: MedlinePlus Genetics (reviewed 2006-11; source updated 2020-09-08).

How it is inherited

This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can inherit disorders resulting from mtDNA mutations only from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.

Most of the body's cells contain thousands of mitochondria, each with one or more copies of mtDNA. The severity of some mitochondrial disorders is associated with the percentage of mitochondria in each cell that has a particular genetic change. Most individuals with NARP have a specific MT-ATP6 mutation in 70 percent to 90 percent of their mitochondria. When this mutation is present in a higher percentage of a person's mitochondria—more than 90 percent to 95 percent—it usually causes a more severe condition known as maternally inherited Leigh syndrome. Because these two conditions result from the same genetic changes and can occur in different members of a single family, and because some individuals with MT-ATP6 gene mutations have related signs and symptoms that do not follow the specific patterns of these conditions, researchers believe that the conditions may be part of a spectrum of overlapping features rather than two distinct syndromes.

Source: MedlinePlus Genetics (reviewed 2006-11; source updated 2020-09-08).

How common it is

MedlinePlus Genetics Frequency

The prevalence of NARP is unknown. This disorder is probably less common than a similar but more severe condition, Leigh syndrome, which affects about 1 in 40,000 people.

Source: MedlinePlus Genetics (reviewed 2006-11; source updated 2020-09-08).

Research studies

3 studies recruiting people with Neuropathy, ataxia, and retinitis pigmentosa.

• North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) (NCT01694940)
• Global Registry and Natural History Study for Mitochondrial Disorders (NCT05554835)
• Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford (NCT01793168)

See all recruiting studies on ClinicalTrials.gov.

Source: ClinicalTrials.gov (retrieved 2026-10-04).

Leigh syndrome

Also known as: Infantile subacute necrotizing encephalopathy, Juvenile subacute necrotizing encephalopathy, Leigh disease, Leigh's disease, Subacute necrotizing encephalomyelopathy.

What is Leigh syndrome?

Leigh syndrome is a severe neurological disorder that usually becomes apparent in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within two to three years, usually due to respiratory failure. A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly.

The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia), which disrupts eating. These problems often result in an inability to grow and gain weight at the expected rate (failure to thrive). Severe muscle and movement problems are common in Leigh syndrome. Affected individuals may develop weak muscle tone (hypotonia), involuntary muscle contractions (dystonia), and problems with movement and balance (ataxia). Loss of sensation and weakness in the limbs (peripheral neuropathy), common in people with Leigh syndrome, may also make movement difficult.

Several other features may occur in people with Leigh syndrome. Many individuals with this condition develop weakness or paralysis of the muscles that move the eyes (ophthalmoparesis); rapid, involuntary eye movements (nystagmus); or degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). Severe breathing problems are common, and these problems can worsen until they cause acute respiratory failure. Some affected individuals develop hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. In addition, a substance called lactate can build up in the body, and excessive amounts are often found in the blood, urine, or the fluid that surrounds and protects the brain and spinal cord (cerebrospinal fluid) of people with Leigh syndrome.

The signs and symptoms of Leigh syndrome are caused in part by patches of damaged tissue (lesions) that develop in the brains of people with this condition. A medical procedure called magnetic resonance imaging (MRI) reveals characteristic lesions in certain regions of the brain. These regions include the basal ganglia, which help control movement; the cerebellum, which controls the ability to balance and coordinates movement; and the brainstem, which connects the brain to the spinal cord and controls functions such as swallowing and breathing. The brain lesions are often accompanied by loss of the myelin coating around nerves (demyelination), which reduces the ability of the nerves to activate muscles used for movement or relay sensory information from the rest of the body back to the brain.

Source: MedlinePlus Genetics (reviewed 2016-05; source updated 2025-03-06).

How it is inherited

Leigh syndrome can have different inheritance patterns. It is most commonly inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. This pattern of inheritance applies to most of the Leigh syndrome-associated genes contained in nuclear DNA, including SURF1. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

In approximately 20 percent of people with Leigh syndrome, the condition is inherited in a mitochondrial pattern. This pattern of inheritance applies to genes contained in mtDNA, including MT-ATP6. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can inherit disorders resulting from mtDNA variants only from their mother. Fathers do not pass traits associated with changes in mtDNA to their children, but when inherited from the mother, these disorders can appear in every generation of a family and can affect both males and females. Each cell has multiple copies of mtDNA. A variant is usually found in only some copies of mtDNA (known as heteroplasmy). The level of heteroplasmy can affect the severity of the condition. In some instances, a variant is found in all copies of mtDNA (known as homoplasmy).

In a small number of affected individuals with variants in nuclear DNA, Leigh syndrome is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a variant would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Occasionally, Leigh syndrome is caused by genetic variants that occur spontaneously, and there is no family history of this condition.

Source: MedlinePlus Genetics (reviewed 2016-05; source updated 2025-03-06).

How common it is

MedlinePlus Genetics Frequency

Leigh syndrome affects at least 1 in 40,000 newborns. The condition is more common in certain populations. For example, the condition 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 individuals on the Faroe Islands.

Source: MedlinePlus Genetics (reviewed 2016-05; source updated 2025-03-06).

Research studies

6 studies recruiting people with Leigh syndrome. Showing the first 5 of 6.

• North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) (NCT01694940)
• Drug Repurposing for Mitochondrial Disorders Using iPSCs Derived Neural Cells (NCT06967831)
• The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism (NCT01780168)
• Global Registry and Natural History Study for Mitochondrial Disorders (NCT05554835)
• Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford (NCT01793168)

See all recruiting studies on ClinicalTrials.gov.

Source: ClinicalTrials.gov (retrieved 2026-10-04).