Delineation of the motor disorder of Lesch-Nyhan disease.
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.
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA. hjinnah@jhmi.edu
H A
HA
Jinnah
Jasper E
JE
Visser
James C
JC
Harris
Alfonso
A
Verdu
Laura
L
Larovere
Irene
I
Ceballos-Picot
Pedro
P
Gonzalez-Alegre
Vladimir
V
Neychev
Rosa J
RJ
Torres
Olivier
O
Dulac
Isabelle
I
Desguerre
David J
DJ
Schretlen
Kenneth L
KL
Robey
Gabor
G
Barabas
Bastiaan R
BR
Bloem
William
W
Nyhan
Raquel
R
De Kremer
Gary E
GE
Eddey
Juan G
JG
Puig
Stephen G
SG
Reich
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D002547:Cerebral Palsy / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003680:Deglutition Disorders / Q000235:genetics / Q000503:physiopathology; D002658:Developmental Disabilities / Q000503:physiopathology; D004401:Dysarthria / Q000235:genetics / Q000503:physiopathology; D004421:Dystonia / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007926:Lesch-Nyhan Syndrome / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009123:Muscle Hypotonia / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D011446:Prospective Studies; D011712:Pyramidal Tracts / Q000503:physiopathology; D012720:Severity of Illness Index