Craniocerebral magnetic resonance imaging measurement and findings in Lesch-Nyhan syndrome

Objective: To provide the first comprehensive magnetic resonance imaging (MRI) assessment of brain in a series of patients with Lesch-Nyhan syndrome (LNS), with emphasis on basal ganglia measurements. Design: Routine readings of MRI studies, repeated reading in random order blinded to subject diagnosis, and 3-dimensional volumetric measures of basal ganglia regions. Setting: The Johns Hopkins Hospital, Baltimore, Md. Patients: Seven patients with LNS who have hypoxanthine guanine phosphoribosyltransferase levels less than 1.6% and characteristic clinical features of the disorder, which include hyperuricemia, cognitive impairment, and dystonic movement disorder, were compared with 7 age-matched control subjects. Five of the 7 patients demonstrated self-injurious behavior. MRI studies were performed using general anesthesia because of the severity of the movement disorder. Main Outcome Measures: Measurement of brain regions from MRI-obtained images. Results: Routine readings described mild cerebral atrophy in 2 of 7 patients, but no caudate or putamen abnormalities were reported. However, on the directed blinded rereading, small caudates were suspected in 5 of 7 cases, and abnormalities in cerebral size and cranium were identified. Volumetric studies of the patients with LNS confirmed a 34% decrease in caudate volume (P<.001), a 17% decrease in total cerebral volume (P<.03), and a 12% decrease in putamen volume (P=. 19). Conclusions: To our knowledge, this is the first demonstration of consistent neuroanatomic abnormalities in LNS. The findings of reduced basal ganglia volume are consistent with the dystonic movement disorder.