Ataxia-oculomotor apraxia type 2

= = Ataxia-Oculomotor Apraxia Type 2 == Ataxia-oculomotor apraxia type 2 (AOA2) is a rare, autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, oculomotor apraxia, and peripheral neuropathy. It is one of the forms of hereditary ataxia and is caused by mutations in the SETX gene.

Clinical Features

Patients with AOA2 typically present with symptoms in late childhood or early adulthood. The main clinical features include:

• Cerebellar Ataxia: This is the most prominent feature and involves a lack of coordination of muscle movements, leading to gait instability and difficulty with fine motor tasks.
• Oculomotor Apraxia: This refers to difficulty in making voluntary eye movements, particularly saccades, which are rapid movements of the eye between fixation points.
• Peripheral Neuropathy: Patients may experience sensory and motor neuropathy, leading to muscle weakness and loss of sensation in the extremities.
• Elevated Serum Alpha-Fetoprotein (AFP): Many patients with AOA2 have elevated levels of AFP, which can be a useful diagnostic marker.

Genetic Basis

AOA2 is caused by mutations in the SETX gene, which encodes the senataxin protein. Senataxin is involved in DNA repair and RNA processing. Mutations in this gene lead to the accumulation of DNA damage, particularly in neurons, contributing to the neurodegenerative process.

Diagnosis

Diagnosis of AOA2 is based on clinical evaluation, family history, and genetic testing. Key diagnostic criteria include:

• Clinical Examination: Assessment of ataxia, oculomotor function, and peripheral neuropathy.
• Genetic Testing: Identification of mutations in the SETX gene confirms the diagnosis.
• Laboratory Tests: Elevated serum AFP levels can support the diagnosis.

Management

There is currently no cure for AOA2, and treatment is primarily supportive. Management strategies include:

• Physical Therapy: To improve coordination and maintain mobility.
• Occupational Therapy: To assist with daily living activities and improve fine motor skills.
• Speech Therapy: For patients with speech difficulties due to ataxia.
• Regular Monitoring: To assess disease progression and manage complications.

Prognosis

The progression of AOA2 is variable, but it generally leads to significant disability over time. Life expectancy may be reduced, but many patients live into adulthood.

Research and Future Directions

Research is ongoing to better understand the pathophysiology of AOA2 and to develop potential therapies. Gene therapy and other molecular approaches are being explored as potential treatments.

See Also

• Hereditary Ataxia
• Oculomotor Apraxia
• Peripheral Neuropathy

,

 Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2, 
 Nature Genetics, 
 2004, 
 Vol. 36(Issue: 3), 
 pp. 225 227, 
 DOI: 10.1038/ng1303,

,

 The Hereditary Ataxias and Related Disorders, 
  
 Churchill Livingstone, 
 1984,

NIH genetic and rare disease info

• NIH info on Ataxia-oculomotor apraxia type 2

Ataxia-oculomotor apraxia type 2 is a rare disease.