It is characterized by cerebellar atrophy and peripheral neuropathy. Sufferers of Type 2 have high amounts of another protein called alpha-fetoprotein (AFP), and may also have high amounts of the protein creatine phosphokinase (CPK). Mutations in the SETX gene are the cause of the disease. AOA2 shows cerebellar atrophy, loss of Purkinje cells, and demyelination. In particular, there is a failure of the cerebrocerebellar circuit in AOA2 that has been shown to be responsible for the weaker coordination of complex cognitive functions such as working memory, executive functions, speech, and sequence learning. Although there is no sign of mental retardation or severe dementia, even after long disease duration, research on families with possible AOA2 have shown mild cognitive impairment as indexed by the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale. These impairments appear to be mostly due to a deficit in initiation and concept subtests,. Ataxia telangiectasia
Telangiectasias are widened blood vessels that can develop anywhere on the skin, mucous membranes, whites of the eyes, and even in the brain. Telangiectasias are associated with multiple systemic signs, the most serious of which are unusual sensitivity to ionizing radiation, excessive chromosomal breakage, and a deficiency in the immune system. Ataxia telangiectasia results from defects in the ataxia telangiectasia mutated gene, which can cause abnormal cell death in various places of the body, including brain areas related to coordinated movement of the eyes. Patients with ataxia telangiectasia have prolonged vertical and horizontal saccade latencies and hypometric saccades, and, although not all, some patients show head thrusts,.
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.