*5.3.3 Ataxia with oculomotor apraxia type 1 (AOA1) and type 2 (AOA2)*

Both recessive conditions manifest as the main clinical features of ataxia and oculomotor apraxia. AOA1 is caused by mutations in the APTX gene which encodes a nuclear protein called aprataxin that is involved in DNA repair [62]. Ataxia usually begins during the first decade of life and is often associated with neuropathy, chorea, nystagmus, and oculomotor apraxia [62]. AOA1 patients do not have extra neurological manifestations. Most AOA1 patients lose the ability to walk independently approximately 7–10 years after the first symptoms [7]. Hypoalbuminemia and hypercholesterolemia are frequent [63].

AOA2 is caused by mutations in the SETX gene which encodes the synthesis of senataxin, a helicase considered to be involved in the defence against DNA damage [64]. Usually, the onset of the disease occurs between 12 and 22 years of age (later than AOA1) [65]. The most frequent presenting manifestation is cerebellar ataxia, which is slowly progressive. Oculomotor apraxia may be absent. Other clinical manifestations include strabismus, sensorimotor peripheral neuropathy and different movement disorders (specially chorea and dystonia) [64, 65]. Elevated serum AFP levels are characteristic, and creatine kinase (CK) levels are occasionally elevated. Cerebellar atrophy appears to be an early sign of AOA2, which stabilises after several years after disease onset [64].
