Enzyme Defect Associated with a Sex-Linked Human Neurological Disorder and Excessive Purine Synthesis
J. Edwin Seegmiller 1,
Frederick M. Rosenbloom 1, and
William N. Kelley 1
1 Section on Human Biochemical Genetics, National Institute of Arthritis and Metabolic Diseases, Bethesda, Maryland 20014
A sex-linked familial neurological disease consisting of cerebral palsy, mental retardation, choreoathetosis, and compulsive aggressive behavior is associated with a loss of an enzyme that participates in purine metabolism, namely, hypoxanthine-guanine phosphoribosyltransferase. The production of excessive uric acid in this disorder implies that the enzyme is involved in the normal regulation of purine biosynthesis. This is the first example of a relation between a specific enzyme defect and abnormal compulsive behavior. It is also the first enzyme defect in purine metabolism demonstrated in a neurological disease.
