Ataxia with oculomotor apraxia type 2: A clinical and genetic study of 19 patients

Published:January 13, 2009DOI:


      Ataxia with oculo-motor apraxia type 2 (AOA2) is a recently described autosomal recessive cerebellar ataxia (ARCA) caused by mutations in the senataxin gene (SETX).
      We analysed the phenotypic spectrum of 19 AOA2 patients with mutations in SETX, which seems to be the third most frequent form of ARCA in Algeria after Freidreich ataxia and Ataxia with vitamin E deficiency. In AOA2 patients, the mean age at onset for all families was in the second decade. Cerebellar ataxia was progressive, slowly leading to disability which was aggravated by axonal polyneuropathy present in almost all the patients. Mean disease duration until wheelchair was around 20 years. Oculo-motor apraxia (OMA) was present in 32% of the patients while convergent strabismus was present in 37%. Strabismus is therefore also very suggestive of AOA2 when associated with ataxia and polyneuropathy even in the absence of OMA. Cerebellar atrophy was more severe in the eldest patients; however it may also be an early sign since it was present in the youngest and paucisymptomatic patients. The initial sign was gait ataxia in all but two patients who presented with head tremor and writer cramp, respectively. Serum alpha-fetoprotein, which was elevated in all tested patients, was a good marker to suggest molecular studies of the SETX gene.


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        • Koenig M.
        • Sirugo G.
        • Duclos F.
        Molecular genetics and familial ataxia.
        Rev Neurol (Paris). 1993; 149: 698-702
        • Cavalier L.
        • BenHamida C.
        • Amouri R.
        • Belal S.
        • Bomont P.
        • Lagarde N.
        • et al.
        Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families.
        Am J Hum Genet. 1998; 62: 301-310
        • Barbot C.
        • Coutinho P.
        • Chorao R.
        • Ferreira C.
        • Barros J.
        • Fineza I.
        • et al.
        Recessive ataxia with ocular apraxia: review of 22 Portuguese patients.
        Arch Neurol. 2001; 58: 201-205
        • Shimazaki H.
        • Takiyama Y.
        • Sakoe K.
        • Ikeguchi K.
        • Niijima K.
        • Kaneko J.
        • et al.
        Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations.
        Neurology. 2002; 59: 590-595
        • Nemeth A.H.
        • Bochukova E.
        • Dunne E.
        • Huson S.M.
        • Elston J.
        • Hannan M.A.
        • et al.
        Autosomal recessive cerebellar ataxia with oculomotor apraxia (ataxia telangiectasia-like syndrome) is linked to chromosome 9q34.
        Am J Hum Genet. 2000; 67: 1320-1326
        • Bomont P.
        • Watanabe M.
        • Gershoni-Barush R.
        • Shizuka M.
        • Tanaka M.
        • Sugano J.
        • et al.
        Homozygosity mapping of spinocerebellar ataxia with cerebellar atrophy and peripheral neuropathy to 9q33–34, and with hearing impairment and optic atrophy to 6p21–23.
        Eur J Hum Genet. 2000; 8: 986-990
        • Moreira M.C.
        • Klur S.
        • Watanabe M.
        • Nemeth A.H.
        • Le Ber I.
        • Moniz J.C.
        • et al.
        Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2.
        Nat Genet. 2004; 36: 225-227
        • Suraweera A.
        • Becherel O.J.
        • Chen P.
        • Rundle N.
        • Woods R.
        • Nakamura J.
        • et al.
        Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage.
        J Cell Biol. 2007; 177: 969-979
        • Lagier-Tourenne C.
        • Tazir M.
        • López L.C.
        • Quinzii C.M.
        • Assoum M.
        • Drouot N.
        ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.
        Am J Hum Genet. 2008; 82: 661-672
        • Vallat J.M.
        • Magy L.
        • Lagrange E.
        • Sturtz F.
        • Magdelaine C.
        • Grid D.
        • et al.
        Diagnostic value of ultrastructural nerve examination in Charcot-Marie-Tooth disease: two CMT 1B cases with pseudo-recessive inheritance.
        Acta Neuropathol. 2007; 113: 443-449
        • Le Ber I.
        • Bouslam N.
        • Rivaud-Pechoux S.
        • Guimaraes J.
        • Benomar A.
        • Chamayou C.
        • et al.
        Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients.
        Brain. 2004; 127: 759-767
        • Duquette A.
        • Roddier K.
        • McNabb-Baltar J.
        • Gosselin I.
        • St-Denis A.
        • Dicaire M.J.
        • et al.
        Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy.
        Ann Neurol. 2005; 57: 408-414
        • Criscuolo C.
        • Chessa L.
        • Di Giandomenico S.
        • Mancini P.
        • Saccà F.
        • Grieco G.S.
        • et al.
        Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study.
        Neurology. 2006; 25: 1207-1210
        • Nadeau J.H.
        Modifier genes in mice and humans.
        Nat Rev Genet. 2001; 2: 165-174
        • Anheim M.
        • Fleury M.C.
        • Franques J.
        • Moreira M.C.
        • Delaunoy J.P.
        • Stoppa-Lyonnet D.
        • et al.
        Clinical and molecular findings of ataxia with oculomotor apraxia type 2 in 4 families.
        Arch Neurol. 2008; 65: 958-962