jueves, 21 de junio de 2018

Neuropathy, Ataxia and Retinitis Pigmentosa (NARP Syndrome)

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By Gaea Marelle Miranda, BA

Neuropathy, ataxia and retinitis pigmentosa, also known as NARP syndrome, is a rare genetic condition characterized by numerous signs and symptoms which affect the nervous system. People with NARP typically experience tingling, numbness, or pain in the arms or legs, problems with balance or ataxia, muscle weakness, and loss of vision.

With NARP being a genetic and inheritable condition, both children and adults may be affected. In children with NARP, global developmental delays or intellectual disabilities are common, whereas the adults affected with the condition are most likely to experience dementia, hearing loss, seizures, and cardiac conduction defects. Signs and symptoms of NARP vary across individuals, hence a precise and direct treatment is yet to be developed.

Causes and Symptoms of NARP Syndrome

NARP is caused by mutations in the MT-ATP6 gene that is contained in the mitochondrial DNA (mtDNA). While the main function of mitochondria is energy production, it also contains a small amount of DNA. The MT-ATP6 gene is responsible for ensuring efficient mitochondrial function through regular protein production and formulation of ATP synthase, the last step in the creation of adenosine triphosphate (ATP), which is the cell’s main source of energy. When mutations in the MT-ATP6 gene develop, the ability of mitochondria to create enough ATP reduces.

While no clear link has been established, abnormal energy production in the mitochondria has been found to develop symptoms related to NARP. However, individuals diagnosed with NARP would also have 70-80% of mutated mtDNA. Research has also found that NARP is a maternally-inherited syndrome that could also be associated with other mitochondrial conditions such as Leigh Syndrome. Possibility for the members of a single family to experience both the conditions is postulated.

People with NARP usually present with the following symptoms:

Problems with balance and coordination (ataxia)
Pain, tingling, or numbness in the arms and legs (sensory neuropathy)
Nerve diseases outside the central nervous system (peripheral neuropathy)
Loss of vision caused by changes in light-sensitive tissues or by retinitis pigmentosa

Apart from these main presentations, people with NARP may also experience seizures, dementia, short stature, hearing loss, and defects in cardiac conduction. Children with this condition are also more prone to delayed development and intellectual disabilities which would greatly impact their functional abilities.

Diagnosing NARP Syndrome

Genetic testing is the primary means to diagnose NARP syndrome. While unique clinical presentations would often indicate the possibility of the condition, only genetic testing would confirm the diagnosis. A variety of molecular genetic tests are available to diagnose NARP, including mutation scanning of exons, targeted variant analysis, sequence analysis of the entire coding region, sequence analysis of selected exons, and deletion or duplication analysis. These tests would look into the functionality of the MT-ATP6 gene and some possible associated mutations.

Apart from genetic testing, physicians would oftentimes triangulate results from laboratory tests, presented symptoms, medical history, and physical examination to come up with a diagnosis of NARP. Therefore, results of genetic tests are only usually confirmatory.

Treating NARP Syndrome

There are currently no proven therapies which could directly address NARP. Usually, treatments are directed to the symptoms and not to the condition. As such, a person with NARP would undergo a series of therapeutic interventions targeted at each particular symptom, such as ophthalmologic treatment for vision problem, psychotherapeutic support for developmental disorders or cognitive difficulties, and neurologic treatment for the enhancement of brain functions. Apart from these, genetic counselling is usually recommended for families affected with the condition.

Also, investigational therapies and clinical trials are currently being conducted to address the condition. Furthermore, lots of support groups for people experiencing NARP and other related conditions have been put up to help individuals who are seeking relief from the emotional and physical burden brought about by this rare condition.

Reviewed by HH Patel, M.Pharm.