Metabolic Disease

Purines and pyrimidines are chemicals that form the nucleic acids (DNA and RNA). An important purine compound is adenosine triphosphate (ATP), which is used to transfer chemical energy for processes such as biosynthesis and transport. There are several rare defects in the synthesis of purines and pyrimidines. The most common symptom of purine overproduction is gout, which arises for several reasons, often not associated with an identifiable enzyme defect but rather due to an imbalance between purine synthesis and disposal. Gout manifests when the ultimate product of purine degradation, uric acid, accumulates and crystallizes in the joints.

A very dramatic disorder of purine metabolism is Lesch-Nyhan syndrome, which is due to a defect in the enzyme hypoxanthine phosphoribosyltransferase (HPRT), resulting in defective salvage of purines and, accordingly, in an increase in the excretion of uric acid. For reasons that are still incompletely understood, a severe defect of HPRT also causes brain-neurotransmitter dysfunction, resulting in a severe spastic form of movement disorder and also a stereotypical compulsion for self-injurious behavior. The concentration of uric acid can be reduced by using the drug allopurinol, but there is no satisfactory treatment for the neurological symptoms associated with Lesch-Nyhan disease.