Ataxia with oculomotor apraxia type 1
What is AOA1?
Ataxia with oculomotor apraxia type 1 (AOA1) is characterized by childhood onset of a slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. The first manifestation is progressive gait imbalance (age of onset: 2-10 years), followed by dysarthria, then upper-limb dysmetria with mild intention tremor. Oculomotor apraxia, usually noticed a few years after the onset of ataxia, progresses to external ophthalmoplegia. All affected individuals have generalized areflexia followed by a peripheral neuropathy and quadriplegia with loss of ambulation about seven to ten years after onset. Hands and feet are short and atrophic. Chorea and upper-limb dystonia are common. Intellect remains normal in some individuals; in others, different degrees of cognitive impairment have been observed.
The diagnosis of AOA1 is based on clinical findings (including family history) and exclusion of the diagnosis of ataxia-telangiectasia. Cerebellar atrophy is visible on MRI in all affected individuals. EMG reveals axonal neuropathy in 100% of individuals with AOA1. Molecular genetic testing of APTX, the only gene associated with AOA1, is clinically available.
AOA1 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being neither affected nor a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if both the disease-causing alleles in a family are known.
Treatment of manifestations: may include physical therapy, particularly for disabilities resulting from peripheral neuropathy; a wheelchair for mobility, usually by age 15-20 years; educational support for difficulties with speaking, reading, and writing. Prevention of secondary complications: high-protein diet to prevent edema by restoring serum albumin concentration; low-cholesterol diet. Surveillance: routine follow-up with a neurologist.
Ataxia with oculomotor apraxia type 2
What is AOA2?
Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between the ages of three and 30, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum concentration of alpha-fetoprotein (AFP).
The diagnosis of AOA2 is based on clinical and biochemical findings, family history, and exclusion of the diagnosis of ataxia-telangiectasia and AOA1. AOA2 is associated with mutations in the gene SETX, which encodes the protein senataxin. Molecular genetic testing is available on a clinical basis.
AOA2 is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. No laboratories offering prenatal testing are listed in the GeneTests Laboratory Directory; however, such testing may be available through laboratories offering custom prenatal diagnosis.
Treatment of manifestations: physical therapy for disabilities resulting from peripheral neuropathy; wheelchair for mobility as needed; educational support (e.g., computer with speech recognition and special keyboard for typing) to compensate for difficulties in reading (caused by oculomotor apraxia) and in writing (caused by upper-limb ataxia). Surveillance: routine follow-up with a neurologist.