Brain Advance Access originally published online on March 20, 2006
Brain 2006 129(5):1201-1217; doi:10.1093/brain/awl056
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Delineation of the motor disorder of Lesch–Nyhan disease
1 Departments of Neurology, Pediatrics, Psychology, and Psychiatry, Johns Hopkins Hospital, 2 Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, 3 The Matheny School and Hospital, Peapack, NJ, 4 Department of Pediatrics, University of California San Diego, La Jolla, CA, 5 Department of Neurology, University of Iowa, Iowa City, IO, USA, 6 Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, 7 Departments of Internal Medicine, Clinical Biochemistry, and Pediatric Neurology, Hospital La Paz, Universidad Autonoma, 8 Department of Pediatric Neurology, Hospital Universitario Gregorio Maranon, Madrid, Spain, 9 Centro de Estudio de las Metabolopatias Congenitas, Universidad Nacional de Cordoba, Cordoba, Argentina, 10 Departments of Medical Biochemistry, Pediatrics and Neurology, Hopital Necker-Enfants Malades, Paris, France and 11 Departments of Chemistry and Biochemistry, Medical University, Sofia, Bulgaria
Correspondence to: H. A. Jinnah, MD, PhD, Meyer Room 6-181, Department of Neurology, Johns Hopkins Hospital, Baltimore, MD 21287, USA E-mail: hjinnah{at}jhmi.edu
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.
Key Words: cerebral palsy; choreoathetosis; dystonia; neurogenetics
Abbreviations: HPRT = hypoxanthine-guanine phosphoribosyltransferase; LND = Lesch–Nyhan disease
Received August 25, 2005. Revised January 17, 2006. Accepted February 13, 2006.