Neurobehavioral features

This figure illustrates a popular model of the basal ganglia. Basically, two parallel pathways exist trough the basal ganglia. Abbreviations: GPe, globus pallidus externa; GPi, globus pallidus interna; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata; STN, subthalamic nucleus.

The processes by which the defect in the hprt gene leads to changes in the brain that cause the problems we see in people with Lesch-Nyhan disease are not well understood. Recent research has focussed on the operations of a region of the brain known as the "basal ganglia". This region is a network of connected structures located at the base of the cortex. The relevant structures include the caudate, putamen, accumbens, globus pallidus, substantia nigra, and parts of the thalamus. The major circuit of the basal ganglia (figure) has been linked to the control of movement, but several additional circuits have been linked to mental abilities and behavioral patterns.

Diseases of the basal ganglia often combine abnormalities of motor control, cognitive impairment, and behavioral change. Some common diseases of the basal ganglia include Huntington’s disease, Parkinson disease, and Tourette syndrome. A growing body of evidence has suggested that many of the problems of Lesch-Nyhan disease also result from dysfunction of the basal ganglia. Their difficulties with motor control, dystonia and chorea, are typically associated with dysfunction of the motor circuit of the basal ganglia. Studies of other diseases and animals have linked the problem of self-injurious behavior to the basal ganglia as well. Their pattern of cognitive impairments may reflect dysfunction of the cognitive circuits of the basal ganglia, but may also reflect broad involvement of the cerebral cortex.

Standard brain scans (MRI and CT) of people with Lesch-Nyhan disease often appear normal, but close inspection may reveal shrinkage of two basal ganglia structures, the caudate and putamen. Also more sophisticated scans and biochemical studies have suggested abnormal basal ganglia function. In particular, shortage of dopamine seems to play an important role. Dopamine is a neurotransmittor, a brain chemical which is involved in signalling between brain cells.