What are the other Names for this Condition? (Also known as/Synonyms)

• NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) Syndrome
• Neurogenic Muscle Weakness, Ataxia, and Retinitis Pigmentosa

What is Neuropathy, Ataxia, and Retinitis Pigmentosa? (Definition/Background Information)

• Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) is a rare genetic condition that causes a gradual deterioration of the nervous system in children and young adults
• Individuals with NARP Syndrome experience numbness, tingling sensation or pain in the legs and arms (sensory neuropathy), muscle weakness associated with balance and coordination problems (ataxia), and degradation of light-sensing cells of the retina leading to blindness (retinitis pigmentosa)
• There is currently no cure and preventive measures available for Neuropathy, Ataxia, and Retinitis Pigmentosa; however, symptomatic treatment and medications can be provided
• The average life expectancy of an individual with NARP Syndrome varies and is based on treatment effectiveness and the rate of neural degradation

Who gets Neuropathy, Ataxia, and Retinitis Pigmentosa? (Age and Sex Distribution)

• Neuropathy, Ataxia, and Retinitis Pigmentosa is a rare disorder estimated to have a prevalence of about 1 in 100,000 live births. It is a congenital condition and newborns are born with the condition. But, the symptoms may not become apparent until late childhood or into early adulthood, depending on the severity of NARP
• Both males and females are affected by NARP Syndrome
• The condition is observed worldwide; no racial or ethnic preference is noted

What are the Risk Factors for Neuropathy, Ataxia, and Retinitis Pigmentosa? (Predisposing Factors)

• The most important risk factor for Neuropathy, Ataxia, and Retinitis Pigmentosa is inherited genetic mutation

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Neuropathy, Ataxia, and Retinitis Pigmentosa? (Etiology)

Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) is an inherited disorder that is caused by a mutation in the MT-ATP6 gene of the mitochondrial DNA.

• The MT-ATP6 gene encodes for a protein that is part of the ATP synthase complex, which is responsible for driving ATP (a cell’s primary energy source) production in cells
• Due to the mutations in the ATP synthase genes, the efficiency of energy production in cells is greatly reduced. The decrease in energy availability mainly affects tissues with high demands for energy, including the muscles, cerebrum, and retina
• The decrease in energy supply to the cerebrum and muscles can lead to balance and coordination problems (ataxia) due to muscle weakness, and the decrease in energy to supply to the retina can cause degradation of light-sensing cells, resulting in blindness (retinitis pigmentosa)
• NARP Syndrome results from maternal transmission. The female egg cells contain organelles called mitochondria that drive energy production. Mitochondria are not present in the male sperm cells. Since only the mother passes mitochondria onto her children, mitochondrial DNA conditions are only caused by maternal transmission

Individuals with Neuropathy, Ataxia, and Retinitis Pigmentosa may have up to 70-95% of their mitochondria affected by mutation. The severity of the disorder is proportional to the percentage of mitochondria affected.

What are the Signs and Symptoms of Neuropathy, Ataxia, and Retinitis Pigmentosa?

The signs and symptoms of Neuropathy, Ataxia, and Retinitis Pigmentosa tend to appear from early childhood or early adulthood, and they gradually increase as the individual gets older. The common signs and symptoms of NARP Syndrome include:

• Intellectual function may be impeded in individuals with NARP
• Muscle weakness, problems with balance and coordination
• Numbness, tingling sensation, and pain in the arms and legs
• Impaired cognitive function, hearing loss, partial or total vision loss
• Developmental delays and learning disabilities are common in childhood NARP-onset, short-stature
• Seizures
• Dementia, mild anxiety disorders
• Electrical abnormalities of the heart
• Episodes of deterioration may occur due to viral illnesses

How is Neuropathy, Ataxia, and Retinitis Pigmentosa Diagnosed?

A diagnosis of Neuropathy, Ataxia, and Retinitis Pigmentosa may involve:

• Screening the family medical history and a complete neurological exam
• Neurological testing (electromyography and nerve conduction) to test for neuropathy
• MRI scan of the brain to view a size decrease (atrophy) in the cerebrum and cerebellum
• Eye examinations to view retina deterioration
• Genetic testing to see if the MT-ATP6 gene is mutated
• Differential diagnosis to rule-out conditions, such as Leigh syndrome and Leigh-like syndrome, which have similar signs and symptoms.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Neuropathy, Ataxia, and Retinitis Pigmentosa?

Neuropathy, Ataxia, and Retinitis Pigmentosa is a progressive and irreversible disorder. The deterioration of the muscles, cerebral region, and retina may be episodic. The complications that may arise include:

• Acidosis (increased acidity of blood) due to lactic acid buildup caused by seizures or decreased aerobic energy production
• Dystonia - involuntary muscle contractions causing repetitive, painful movements
• Cardiomyopathy (condition caused by abnormal heart muscle) leading to decreased blood flow, with a potential for heart failure

How is Neuropathy, Ataxia, and Retinitis Pigmentosa Treated?

Currently, there is no cure for Neuropathy, Ataxia, and Retinitis Pigmentosa. Relief from pain, symptoms, and stress of the disorder can be sought through the following measures:

• Sodium bicarbonate or sodium citrate to neutralize acidosis
• Antiepileptic drugs to treat specific types of seizures
• Antioxidants to improve energy production
• Muscle relaxants to ease dystonia
• Medications to prevent heart failure and ease cardiomyopathy

How can Neuropathy, Ataxia, and Retinitis Pigmentosa be Prevented?

• Currently, there are no specific methods or guidelines to prevent Neuropathy, Ataxia, and Retinitis Pigmentosa, since it is a genetic condition
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Neuropathy, Ataxia, and Retinitis Pigmentosa? (Outcomes/Resolutions)

• Currently,  Neuropathy, Ataxia, and Retinitis Pigmentosa is a genetic condition that cannot be cured
• The life expectancy of an individual with NARP Syndrome varies and is based upon the percentage of mitochondrial DNA affected by mutation

Additional and Relevant Useful Information for Neuropathy, Ataxia, and Retinitis Pigmentosa:

Although, currently there is no cure for Neuropathy, Ataxia, and Retinitis Pigmentosa, the following extensive researches are being undertaken:

• Using gene replacement therapy to eliminate the mutant mitochondrial DNA or nuclear transfer into a donor, in order to prevent mutated mitochondrial DNA from being passed down to children
• Antioxidants are also being explored as a means to help treat mitochondrial disorders by helping to improve the energy production
• Clinical trials are currently ongoing