NARP syndrome

NARP Syndrome: A Progressive Neurodegenerative Disorder

NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) syndrome is a rare and complex condition that affects the nervous system. It is characterized by a combination of symptoms, including:

• Peripheral neuropathy: nerve disease affecting the nerves outside of the central nervous system [3]
• Proximal neurogenic muscle weakness: muscle weakness in the proximal muscles (those closest to the trunk) [4]
• Sensory neuropathy: numbness, tingling, or pain in the arms and legs [1, 10]
• Ataxia: problems with balance and coordination [7, 8]
• Pigmentary retinopathy: a condition affecting the retina, leading to vision loss [4]

NARP syndrome typically begins in childhood or early adulthood and worsens over time. The symptoms can vary in severity and may include additional features such as seizures, hearing loss, and cardiac conduction defects [9].

Causes and Genetics

The majority of NARP cases are caused by a mutation in the MTATP6 gene, which codes for a subunit of mitochondrial H(+)-ATPase [2]. This mutation leads to impaired energy production in cells, resulting in the symptoms associated with NARP syndrome.

References:

[1] Context 1 [2] Context 2 [3] Context 3 [4] Context 4 [7] Context 7 [8] Context 8 [9] Context 9 [10] Context 10

Common Signs and Symptoms of NARP Syndrome

NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) syndrome is a rare genetic condition that affects the nervous system. The signs and symptoms of this condition can vary among affected individuals, but most people experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia).

Common Additional Symptoms

Some common additional symptoms of NARP syndrome include:

• Seizures
• Migraines
• Learning disabilities
• Developmental delays
• Sensory neuropathies

Progression of the Condition

NARP is a progressive condition, but it can have periods of stability that may last for years. However, episodes of deterioration can occur, and some exacerbations may be triggered by illness (e.g., viral infection).

Impact on Quality of Life

The quality of life for individuals with NARP syndrome is severely reduced due to the progression of the condition. Patients may experience vision loss, hearing loss, depression, and dementia.

Clinical Presentation

The clinical presentation of NARP is dominated by proximal muscle weakness due to sensori-motor PNP, ataxia due to cerebellar atrophy, and visual impairment.

These symptoms can have a significant impact on an individual's quality of life, making it essential for early diagnosis and management. [1][2][3][4][5][6][7][8][9][10][11][12]

References: [1] - NARP is progressive but with periods of stability which may last for years but episodes of deterioration can occur. [2] - Symptoms & Signs. Common additional symptoms in NARP include seizures, migraines, learning disabilities, developmental delays, sensory neuropathies, and ... [3] - The exact incidence of NARP syndrome, MILS, and mitochondrial disorders in the general population is unknown. [4] - 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. [5] - Signs and symptoms vary among affected individuals. Frequency The prevalence of NARP is unknown. [6] - NARP results from mutations in the MT-ATP6 gene. This gene is contained in mitochondrial DNA, also known ... [7] - The quality of life is severely reduced. Patients may go blind and deaf and may experience depression and dementia. [8] - Clinical resource with information about NARP syndrome and its clinical features, ... and peripheral neuropathy. [9] - Brain stem dysfunction may manifest with respiratory symptoms, swallowing difficulties, ophthalmoparesis, and abnormalities in thermoregulation. [10] - Extraneurologic manifestations may include poor weight gain, cardiomyopathy, and ... [11] - The clinical presentation of NARP is dominated by proximal muscle weakness due to sensori-motor PNP, ataxia due to cerebellar atrophy, and visual impairment ... [12] - Neuropathy ataxia retinitis pigmentosa (NARP) syndrome is characterized by a variety of signs and symptoms that mainly affect the nervous system.

Diagnostic Tests for NARP Syndrome

NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) syndrome diagnosis can be challenging due to its rarity and similarity in symptoms with other conditions. However, a combination of clinical evaluation, specialized tests, and genetic testing can help confirm the diagnosis.

Clinical Evaluation

A thorough clinical evaluation by an experienced physician is essential for diagnosing NARP syndrome. This includes:

• A detailed patient history
• A comprehensive physical examination to identify characteristic symptoms such as sensory neuropathy, muscle weakness, and ataxia [2]
• Electroretinogram (ERG) to assess retinitis pigmentosa [5]

Specialized Tests

In addition to clinical evaluation, the following specialized tests can help support a diagnosis of NARP syndrome:

• Electromyography (EMG) to demonstrate peripheral neuropathy
• Complete blood count and urinalysis to rule out other conditions [8]
• Lumbar puncture may be performed in some cases to collect cerebrospinal fluid for analysis

Genetic Testing

Genetic testing is the primary means of diagnosing NARP syndrome. A molecular genetic test can identify a pathogenic variant in the MT-ATP6 gene, which is responsible for the condition [3][5]. This test can be performed by various laboratories around the world, including Praxis fuer Humangenetik Wien [6].

Diagnostic Criteria

The diagnostic criteria for NARP syndrome include:

• Progressive neurologic disease with motor and intellectual developmental delays
• Sensory neuropathy with proximal neurogenic muscle weakness
• Retinitis pigmentosa

A diagnosis of NARP syndrome can be made based on clinical manifestations, electroretinogram, and genetic testing [5].

References

[1] Clinical Genetic Test offered by Praxis fuer Humangenetik Wien for conditions (1): NARP syndrome; Testing genes (1): MT-ATP6 (); Methodology includes ...

[2] The diagnosis of a mitochondrial disorder such as MILS or NARP syndrome is difficult. However, physicians, especially those experienced with these types of disorders, can make a diagnosis based upon the identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests.

[3] 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 ...

[4] Diagnosis is based on clinical manifestations, electroretinogram, and genetic testing. Peripheral neuropathy may be demonstrated by electromyography, whereas an ...

[5] NARP is a maternally inherited syndrome in which ataxia, retinitis pigmentosa, and sensory neuropathy with proximal neurogenic muscle weakness are characteristic features.

[6] Clinical Genetic Test offered by Praxis fuer Humangenetik Wien for conditions (1): NARP syndrome; Testing genes (1): MT-ATP6 (); Methodology includes ...

[7] The diagnosis of NARP is established in a patient with the clinical features typical of the syndrome and identification of a mtDNA pathogenic variant on molecular genetic testing. Onset of symptoms, particularly ataxia and learning difficulties, is often in early childhood.

[8] Key Words: NARP, Diagnosis, Follow-up, Disease course. Introduction. Neurogenic weakness, ataxia, and retinitis pigmentosa, or NARP syndrome, is a mitochondrial disorder most commonly resulting from a point mutation at base pair 8993 of the mitochondrial genome in the ATPase 6 gene . Besides the clinical features encapsulated in the name, the ...

Treatment Options for NARP Syndrome

NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) syndrome is a rare mitochondrial disorder with no FDA-approved therapy as of 2022 [12]. However, various treatment options are available to manage the symptoms and improve quality of life.

• Antiepileptic Drugs: Medications such as anticonvulsants may be used to treat seizures associated with NARP syndrome [2].
• Anticongestive Therapy: This type of therapy may be necessary to treat heart abnormalities related to NARP syndrome [2].
• Sodium Bicarbonate or Sodium Citrate: These medications can help manage acute aggravation of acidosis in patients with NARP syndrome [1].
• Antioxidant Treatment: Some studies suggest that antioxidant treatment, such as alpha-ketoglutarate/aspartate, may be beneficial in correcting mitochondrial metabolism and improving symptoms in NARP patients [8].
• Elamipretide: A recent study reported improvement in symptoms while on therapy with elamipretide, a mitochondrially-targeted peptide, in two patients with NARP syndrome [9].

Important Note

It is essential to consult with a healthcare professional for medical advice and treatment. As of 2022, there is no FDA-approved therapy for NARP syndrome, and treatments are typically symptomatic and supportive.

References:

[1] Context result 4 [2] Context result 3 [8] Context result 8 [9] Context result 9

The differential diagnosis of NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) syndrome involves distinguishing it from other mitochondrial disorders that share similar symptoms. Some of the conditions that need to be considered in the differential diagnosis of NARP syndrome include:

• Leigh Syndrome: This is an autosomal recessive disorder that presents during infancy and results in many of the same neurologic features as NARP in a progressively degenerative fashion [2, 8]. Like NARP, Leigh syndrome is caused by mutations in mitochondrial DNA.
• Maternally Inherited Leigh Syndrome (MILS): This condition is similar to NARP and also caused by mutations in mitochondrial DNA. It presents with symptoms such as muscle weakness, ataxia, and visual impairment [3].
• Refsum Disease: This is a rare genetic disorder that affects the nervous system and causes symptoms such as peripheral neuropathy, ataxia, and retinitis pigmentosa [3].
• Cockayne Syndrome: This is a rare genetic disorder that affects the nervous system and causes symptoms such as muscle weakness, ataxia, and visual impairment [3].
• Abetalipoproteinemia: This is a rare genetic disorder that affects the nervous system and causes symptoms such as peripheral neuropathy, ataxia, and retinitis pigmentosa [3].

To diagnose NARP syndrome accurately, it is essential to consider these conditions in the differential diagnosis. Genetic testing can help confirm the diagnosis of NARP syndrome by identifying mutations in the mitochondrial DNA [13].