The motor disorder associated with Lesch-Nyhan disease (LND) was studied in a total of 44 patients (ages 2 to 38 years) seen at Johns Hopkins Hospital, Baltimore, MD, and other US and international centers. A characteristic motor syndrome begins with hypotonia and/or delayed motor development in the first 3-6 months of age, and is followed by involuntary movements between 6 and 24 months. The course is then relatively static with severe action dystonia, sometimes associated with choreoathetosis or ballismus, and less frequently, pyramidal signs affecting the lower extremities. The evolution of the motor syndrome of LND parallels the cognitive disability and behavioral syndrome that includes mental retardation and self-injurious behavior. Brain MRI in 25 patients showed cerebral atrophy or maldevelopment in 3, and 34% reduction in basal ganglia volume in 7 compared to normal controls. The results of this large multi-centre prospective study are compared with a review of 122 previous reports, including 254 patients. [1]

COMMENT. LND is an X-linked recessive neurobehavioral disorder of purine metabolism caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). The triad of clinical manifestations, mental retardation, self-injurious behavior, and motor disability, develops after birth, and the extrapyramidal movements are evident in the second year of life. In the present report, hypotonia and dystonia were more frequent than spasticity, noted in earlier descriptions of the syndrome. The authors attribute these discrepancies in neurological findings to a possible misinterpretation of a “striatal toe” as a Babinski reflex, and changes in signs with age, not observed in retrospective studies. In laboratory tests, serum uric acid is elevated, and diagnosis is confirmed by a urinary uric acid-creatine ratio of 2:1 or higher, and enzymatic analysis of blood, cultured skin fibroblasts, or prenatal, amniotic fluid (Menkes JH, 1985).