Brain Advance Access published online on March 20, 2006
Brain, doi:10.1093/brain/awl056
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1 Department of Neurology, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Psychology, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Psychiatry, Johns Hopkins Hospital, Baltimore, MD, USA
* To whom correspondence should be addressed. Lesch-Nyhan disease (LND) is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit over-production of uric acid, along with a characteristic neurobehavioural syndrome that includes mental retardation, recurrent self-injurious behaviour and motor disability. Prior studies involving relatively small numbers of patients have provided different conclusions on the nature of the motor disorder. The current study includes the results of a multi-centre international prospective study of the motor disorder in the largest cohort of patients studied to date. A total of 44 patients ranging from 2 to 38 years presented a characteristic motor syndrome that involved severe action dystonia superimposed on baseline hypotonia. Although some patients also displayed other extrapyramidal or pyramidal signs, these were always less prominent than dystonia. These results are compared with a comprehensive review of 122 prior reports that included a total of 254 patients. Explanations for the differing observations available in the literature are provided, along with a summary of how the motor disorder of LND relates to current understanding of its pathophysiology involving the basal ganglia.
Received August 25, 2005
Revised January 17, 2006
Accepted February 13, 2006
Article
Delineation of the motor disorder of Lesch-Nyhan disease
H. A. Jinnah 1 *,
Jasper E. Visser 2,
James C. Harris 1,
Alfonso Verdu 3,
Laura Larovere 4,
Irene Ceballos-Picot 5,
Pedro Gonzalez-Alegre 6,
Vladimir Neychev 7,
Rosa J. Torres 8,
Olivier Dulac 5,
Isabelle Desguerre 5,
David J. Schretlen 1,
Kenneth L. Robey 9,
Gabor Barabas 9,
Bastiaan R. Bloem 2,
William Nyhan 10,
Raquel De Kremer 4,
Gary E. Eddey 9,
Juan G. Puig 8,
Stephen G. Reich 11,
and
for the Lesch-Nyhan Disease International Study Group
2 Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
3 Department of Internal Medicine, Hospital La Paz, Universidad Autonoma, Madrid, Spain; Department of Clinical Biochemistry, Hospital La Paz, Universidad Autonoma, Madrid, Spain; Department of Pediatric Neurology, Hospital La Paz, Universidad Autonoma, Madrid, Spain; Department of Pediatric Neurology, Hospital Universitario Gregorio Maranon, Madrid, Spain
4 Centro de Estudio de las Metabolopatias Congenitas, Universidad Nacional de Cordoba, Cordoba, Argentina
5 Department of Medical Biochemistry, Hopital Necker-Enfants Malades, Paris, France; Department of Pediatrics, Hopital Necker-Enfants Malades, Paris, France; Department of Neurology, Hopital Necker-Enfants Malades, Paris, France
6 Department of Neurology, University of Iowa, Iowa City, IO, USA
7 Department of Chemistry, Medical University, Sofia, Bulgaria; Department of Biochemistry, Medical University, Sofia, Bulgaria
8 Department of Internal Medicine, Hospital La Paz, Universidad Autonoma, Madrid, Spain; Department of Clinical Biochemistry, Hospital La Paz, Universidad Autonoma, Madrid, Spain; Department of Pediatric Neurology, Hospital La Paz, Universidad Autonoma, Madrid, Spain
9 The Matheny School and Hospital, Peapack, NJ, USA
10 Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
11 Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA
H. A. Jinnah, E-mail: hjinnah{at}jhmi.edu
Abstract 
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