AOA3 is a rare type of autosomal recessive cerebellar ataxia. Other disorders in this group include Spinocerebellar Ataxia, Autosomal Recessive 1, Ataxia with Oculomotor Apraxia Type 1, Ataxia-Telangiectasia and Ataxia-Telangiectasia-Like-Disorder. The disease is characterized by ataxia, dysmetria, peripheral neuropathy, areflexia, cerebellar atrophy, oculomotor apraxia and raised alpha-fetoprotein levels. Symptoms usually surface in the second decade of life and follow a highly rapid progression. Patients may hence become wheelchair-bound by the third or fourth decade of life. AOA3 has so far been diagnosed in only a single Saudi Arab family.
Diagnosis of the disorder is made based on a clinical investigation, the presence of cerebellar atrophy, and levels of alpha-fetoprotein. While the disorder cannot presently be cured, symptoms can be managed by physical therapy, speech therapy, mobility aids and special education.
Al Tassan et al. (2012) described a Saudi family with four individuals affected by Ataxia with Oculomotor Apraxia. The index patient, a 33-year-old male, complained of frequent falls and unsteady legs from the age of 14-years. Subsequently, he suffered from arms dysmetria, truncal ataxia and cerebellar dysarthric speech. He was wheelchair bound by the age of 23-years. Other features included impaired ocular movement, severe limb and axial dysmetria, areflexia, mild distal atrophy and global weakness of the legs. An MRI revealed bilateral atrophy of the cerebella folia with marked vermal atrophy. Three other affected siblings had a similar disease pattern. All four patients showed elevated alpha-fetoprotein levels as well as moderately severe axonal sensory polyneuropathy with absent sensory nerve action potentials in the lower limbs. When no mutations were uncovered in the SETX gene, linkage analysis and homozygosity analysis were employed to map the disease to chromosome 17. Sequencing unveiled a homozygous missense change in the PIK3R5 gene. All affected siblings were homozygous for the mutation while the parents and unaffected siblings were found to be heterozygous.