These are autosomal recessive disorders and the associated gene products are involved in DNA repair. Both horizontal and vertical eye movements are affected in these disorders. Although people with either type may have some mild cognitive problems, such as difficulty with concentration or performing multi-step activities, intellectual function is usually not affected. Type 1
Ataxia-oculomotor apraxia type 1 (AOA1) usually has an onset of symptoms during childhood. It is an autosomal recessive cerebellar ataxia (ARCA) associated with hypoalbuminemia and hypercholesterolemia. Mutations in the gene APTX, which encodes for aprataxin, have been identified to be responsible for AOA1. Elevated creatine kinase is occasionally present, in addition to a sensorimotor axonal neuropathy, as shown by nerve conduction velocity studies. In addition, MRI studies have shown cerebellar atrophy, mild brainstem atrophy, and, in advanced cases, cortical atrophyThe aprataxin protein APTX can remove obstructive termini from DNA strand breaks that interfere with DNA repair. APTX is recruited to DNA single-strand breaks by XRCC1 protein, where it functions as a nick sensor to scan the single-strand breaks for 5’-AMP obstructive termini that are intermediates in failed DNA ligase reactions. The removal of these obstructions allows DNA repair of the break to be completed. It is not yet clear which specific single-strand breaks are the neurodegenerative agents in AOA1 patients that lack functional aprataxin protein. However single-strand breaks with 5’-AMP termini appear to be the most likely candidate lesion. Type 2
Ataxia-oculomotor apraxia type 2 (AOA2), also known as spinocerebellar ataxia with axonal neuropathy type 2, has its onset during adolescence.
Sometimes no cause is found, in which case it is described as idiopathicA person may be born with the parts of the brain for eye movement control not working, or may manifest poor eye movement control in childhood. If any part of the brain that controls eye movement becomes damaged, then OMA may develop. One of the potential causes is bifrontal hemorrhages. In this case, OMA is associated with bilateral lesions of the frontal eye fields (FEF), located in the caudal middle frontal gyrus. The FEF control voluntary eye movements, including saccades, smooth pursuit and vergence. OMA can also be associated with bilateral hemorrhages in the parietal eye fields (PEF). The PEF surround the posterior, medial segment of the intraparietal sulcus. They have a role in reflexive saccades, and send information to the FEF. Since the FEF and PEF have complementary roles in voluntary and reflexive production of saccades, respectively, and they get inputs from different areas of the brain, only bilateral lesions to both the FEF and PEF will cause persistent OMA. Patients with either bilateral FEF or bilateral PEF damage (but not both FEF and PEF) have been shown to regain at least some voluntary saccadic initiation some time after their hemorrhages. Other causes of OMA include brain tumors and cardiovascular problems,. Ataxia with oculomotor apraxia
A subgroup of genetically recessive ataxias associated with OMA has been identified, with an onset during childhood. These are ataxia with oculomotor apraxia type 1 (AOA1), ataxia with oculomotor apraxia 2 (AOA2), and ataxia telangiectasia.