Ataxia with oculomotor apraxia type 2
AOA2

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Description from OMIM

Autosomal recessive spinocerebellar ataxia-1 is a neurodegenerative disorder characterized by juvenile onset of progressive cerebellar ataxia, axonal sensorimotor peripheral neuropathy, and increased serum alpha-fetoprotein (AFP; 104150). Oculomotor apraxia is a common but inconsistent finding, found in about 50% of patients; hence this disorder is sometimes referred to as 'ataxia-oculomotor apraxia-2' (AOA2) (Moreira et al., 2004; summary by Ichikawa et al., 2013). Duquette et al. (2005) emphasized that oculomotor apraxia is not a universal finding in this disorder and suggested the name 'spinocerebellar ataxia, autosomal recessive, with axonal neuropathy-2' (SCAN2) to distinguish it from SCAN1 (607250). For a discussion of genetic heterogeneity of ataxia-oculomotor apraxia, see AOA1 (208920).



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List of symptoms



Symptom/sign Organ system Percent affected Pubmed id Added on(yyyy-mm-dd) Edit/add reference
Ataxia nervous 100 % 19696032 2011-10-27
Increased blood AFP circulatory 99 % 19696032 2011-10-27
Neuropathy nervous 98 % 19696032 2011-10-27
Cerebellar atrophy nervous 96 % 19696032 2011-10-27
Oculomotor apraxia nervous 51 % 19696032 2011-10-27
Tremor nervous 14 % 19696032 2011-10-27
Dystonia nervous 14 % 19696032 2011-10-27
Strabismus nervous 12 % 19696032 2011-10-27
Chorea nervous 10 % 19696032 2011-10-27



List of references:


Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients.
M Anheim, B Monga, M Fleury, P Charles, C Barbot, M Salih, J P Delaunoy, M Fritsch, L Arning, M Synofzik, L Schöls, J Sequeiros, C Goizet, C Marelli, I Le Ber, J Koht, J Gazulla, J De Bleecker, M Mukhtar, N Drouot, L Ali-Pacha, T Benhassine, M Chbicheb, A M'Zahem, A Hamri, B Chabrol, J Pouget, R Murphy, M Watanabe, P Coutinho, M Tazir, A Durr, A Brice, C Tranchant, M Koenig,

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 microg/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 microg/l, P = 0.0004; itself higher than the normal level (3.4 microg/l, range from 0.5 to 17.2 microg/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level > or =7 microg/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels > or =7 microg/l is 46%. Therefore, selection of patients with an AFP level above 7 microg/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy.

Brain : a journal of neurology - Oct 2009