Introduction:
Neuropathy, ataxia, and retinitis pigmentosa (NARP) is a rare disorder that primarily affects the neurological system and causes a variety of signs and symptoms. The indications and symptoms of the disorder frequently deteriorate over time, usually starting in childhood or early adulthood. Most NARP patients experience numbness, tingling, pain in their arms and legs, muscle weakness, and balance and coordination issues.
What Is NARP Syndrome?
NARP syndrome (neuropathy, ataxia, and retinitis pigmentosa) is a rare genetic condition characterized by numerous signs and symptoms affecting the nervous system. Affected individuals may also experience vision loss due to retinitis pigmentosa. Learning disabilities, developmental delays, seizures, dementia, hearing loss, and cardiac conduction defects are also characteristics of NARP. NARP syndrome is caused by genetic changes in the MT-ATP6 gene. This gene is found in mitochondrial DNA (mtDNA). NARP typically manifests in childhood and has an estimated incidence rate of 1 to 9 per 100,000 people. NARP affects both men and women in equal numbers.
What Causes NARP Syndrome?
NARP is caused by mutations in the MT-ATP6 gene. This gene is found in mitochondrial DNA (mtDNA). The MT-ATP6 gene codes for a protein required for normal mitochondrial function. Through a series of chemical reactions, mitochondria produce adenosine triphosphate (ATP), the cell's primary energy source. The MT-ATP6 protein is a subunit of the ATP synthase enzyme, which controls the final step in ATP production. Mutations in the MT-ATP6 gene change the structure or function of ATP synthase and result in reduced mitochondrial ATP production.
How Is NARP Syndrome Inherited?
NARP syndrome is inherited through mitochondrial inheritance (maternal inheritance). This inheritance pattern applies to genes found in mtDNA.Children can only inherit illnesses brought on by mtDNA mutations from their mother since only egg cells, not sperm cells, give mitochondria to the growing embryo. Both men and women can be affected by these illnesses, which can run in families through all generations. However, fathers do not convey features linked to mtDNA mutations to their offspring. The severity of mitochondrial disorders is related to the percentage of mitochondria in each cell that has a specific genetic change. The majority of NARP patients have a specific MT-ATP6 mutation in 70 to 90 percent of their mitochondria. When this mutation is present in a higher percentage of a person's mitochondria, more than 90 % to 95 %, it usually results in a more severe condition.
What Are the Symptoms of NARP Syndrome?
Children with NARP frequently exhibit developmental delays and learning impairments, while elderly people with this disorder may lose their intellectual function (dementia). However, the signs and symptoms associated with NARP syndrome may vary among affected individuals. The commonly observed symptoms of NARP syndrome are the following.
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Ataxia.
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Blindness.
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Babinski sign.
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Cerebral atrophy.
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Constriction of the visual field.
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Developmental delay.
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Hearing impairment.
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Headache.
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Muscle spasm.
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Muscle weakness.
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Short stature.
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Seizure.
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Sensory neuropathy.
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Optic disc pallor.
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Myoclonic spasms.
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Irritability.
How Is NARP Syndrome Diagnosed?
NARP syndrome is primarily diagnosed through genetic testing. While unusual clinical manifestations frequently indicate the presence of the condition, only genetic testing can confirm the diagnosis. To diagnose NARP, several molecular genetic tests are available, including exon mutation scanning, sequence analysis of the entire coding region, targeted variant analysis, deletion or duplication analysis, and sequence analysis of selected exons.
A complete blood count (CBC), urinalysis, and lumbar puncture are other potentially useful tests that can help differentiate NARP syndrome from other disorders. Brain MRI (magnetic resonance imaging) and computerized tomography (CT) may show cerebral and cerebellar atrophy as well as basal ganglia abnormalities. Arrhythmias and cardiomyopathies can be detected using an electrocardiogram and echocardiogram. Peripheral neuropathy can be assessed using electromyography and nerve conduction studies.
What Are the Treatment Options Available for NARP Syndrome?
As of now, there are no effective treatments that could specifically target NARP. The majority of the treatment options available focus on the symptoms rather than the underlying cause. As a result, a person with NARP syndrome would undergo a series of therapeutic interventions targeted at each specific symptom, such as ophthalmologic treatment, psychotherapeutic support for cognitive challenges or developmental disorders, and neurologic treatment for the improvement of brain functions. Families affected by the illness are typically advised to seek genetic counseling in addition to this.
- Medical Therapy: The majority of NARP syndrome treatments are supportive, such as medications for acute acidosis (Sodium bicarbonate or Sodium citrate), anticonvulsants, medications for dystonia ( Baclofen and Gabapentin), and treatments for cardiomyopathy. Frequent monitoring (every 6 to 12 months) and emotional support may be beneficial. Barbiturates, dichloroacetate, sodium valproate, and anesthetics are a few drugs that are contraindicated in NARP syndrome patients.
- Genetic Counseling: NARP syndrome is a mitochondrial disease that is passed down from mothers to their children. The number of mutations becomes an important factor in determining the clinical severity of the disease in offspring. Women should be counseled about the possibility of variable NARP expressivity due to the genetic shift from mother to offspring. Amniocentesis and prenatal chorionic villus sampling with cytogenetic analysis can be used to identify mutations in the fetus if there is a family history of NARP syndrome. Another method for detecting mutations is preimplantation genetic diagnosis.
What Is the Differential Diagnosis of NARP Syndrome?
NARP syndrome must be distinguished from other mitochondrial illnesses as they have many similar symptoms (particularly Leigh syndrome). Many of the same neurologic characteristics as NARP syndrome are seen in the autosomal recessive disorder Leigh syndrome, which manifests in infancy and progresses in a degenerative manner. Motor regression, loss of appetite, vomiting, seizures, widespread weakness, hypotonia, and episodes of lactic acidosis are examples of classic symptoms. Various ataxia disorders, retinitis pigmentosa, Charcot-Marie-Tooth hereditary neuropathy, pyruvate dehydrogenase deficiency, and biotinidase deficiency are other disorders that may have similar symptoms as that of NARP syndrome.
Conclusion:
NARP (neuropathy, ataxia, retinitis pigmentosa) syndrome is a rare neurodegenerative disease. It is a mitochondrial disorder caused by a point mutation in the MT-ATP6 gene. Typical symptoms of NARP include tingling, numbness, or discomfort in the arms or legs, ataxia or balance issues, muscle weakness, and visual loss. The signs and symptoms of NARP syndrome vary from person to person, and treatment is primarily focused on the management of symptoms.
