Spinocerebellar ataxia type 3 presenting as an L-DOPA responsive dystonia phenotype in a Chinese family E. Wilder-Smith a, * , E.K. Tan b , H.Y. Law c , Y. Zhao d , I. Ng c , M.C. Wong b a Division of Neurology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore b Department of Neurology, Singapore General Hospital, Singapore c Genetic Service, KK Women and Children Hospital, Singapore d Department of Clinical Research, Singapore General Hospital, Singapore Received 22 January 2003; received in revised form 8 April 2003; accepted 18 April 2003 Abstract The clinical spectrum of spinocerebellar ataxia 3 (SCA 3) disease is wide and varied. We describe a Chinese patient with a mutation at the SCA 3 locus with clinical features of levodopa-responsive dystonia. The family history was suggestive of being autosomally dominant. Levodopa responsiveness though rare has been described in families with features of parkinsonism. Noteworthy is the relatively late onset of disease (>40 years) possibly explained by the low number of affected alleles at 59, the usual range being from 62 to 86, with the lowest recorded number at 56. This expands the wide and varied phenotypic manifestations of SCA 3, and highlights the observation that features suggestive of levodopa-responsive dystonia (DRD) such as focal dystonia, gait difficulty with diurnal fluctuation of symptoms, and a marked response to low doses of levodopa can be presenting features of SCA 3. SCA 3 should be considered a differential diagnosis in adult patients who present with DRD phenotype and with a positive family history. D 2003 Elsevier Science B.V. All rights reserved. Keywords: Spinocerebellar atrophy; SCA 3; Phenotype; L-DOPA sensitive Dystonia 1. Introduction Spinocerebellar ataxia 3 (SCA 3) (Machado–Joseph disease), once thought to be of Azorean origin, has been widely described amongst various ethnic populations around the globe and appears to be one of the most common forms of autosomal dominant cerebellar ataxia [1–3]. Multiple SCA 3 phenotypes have been described. These include combinations of extrapyramidal and pyramidal signs or cerebellar and pyramidal tract signs, cerebellar signs with anterior horn cell degeneration, and rarely, levodopa-respon- sive parkinsonism with or without anterior horn cell degen- eration [1–5]. There was a recent report of SCA 3 in a family of sub- Saharan African descent presenting with clinical features indistinguishable from Parkinson disease and who were levodopa responsive [5]. We describe a Chinese patient with SCA 3 presenting features suggestive of levodopa-respon- sive dystonia (DRD). 2. Case reports A previously well 40 year old Singaporean Chinese woman presented with progressive difficulty in walking associated with cramps of her right lower extremity over a 3-year period. She noted marked diurnal variation of her gait with gradual worsening as the day progressed. With pro- longed walking, both legs (the right being more affected than the left) would cramp, stiffen, and she would have to walk on her toes. After periods of rest longer than half an hour, she would experience significant improvement of gait. She had no tremors, urinary and bowel disturbances, difficulty swal- lowing, speaking and writing, and behavioural or cognitive changes. On examination, there was dystonic posturing of her right leg, and to a lesser extend the left leg, with plantar flexion and inversion of the feet and clawing of the toes upon walking for 5 min. There was no tremor and cog- 0022-510X/03/$ - see front matter D 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S0022-510X(03)00129-1 * Corresponding author. Tel.: +65-6772-4171; fax: +65-6779-4112. E-mail address: mdcwse@nus.edu.sg (E. Wilder-Smith). www.elsevier.com/locate/jns Journal of the Neurological Sciences 213 (2003) 25 – 28