Clinical Information

Purines (adenine, guanine, xanthine, hypoxanthine) and pyrimidines (uracil, thymine, cytosine, orotic acid) are involved in all biological processes, providing the basis for storage, transcription, and translation of genetic information as RNA and DNA. Purines are required by all cells for growth and survival and also play a role in signal transduction and translation. Purines and pyrimidines originate primarily from endogenous synthesis, with dietary sources playing only a minor role. The end product of purine metabolism is uric acid (2,6,8-trioxypurine), which must be excreted continuously to avoid toxic accumulation.

Disorders of purine and pyrimidine metabolism can involve all organ systems at any age. The diagnosis of the specific disorders of purine and pyrimidine metabolism is based upon the clinical presentation of the patient, determination of specific concentration patterns of purine and pyrimidine metabolites, and confirmatory enzyme assays and/or molecular genetic testing.

There are numerous inborn errors of purine and pyrimidine metabolism that have been documented. Clinical features are dependent upon the specific disorder, but represent a broad spectrum of clinical manifestations that may include immunodeficiency, developmental delay, nephropathy, and neurologic involvement. The most commonly described disorder involves a deficiency of hypoxanthine phosphoribosyl transferase (HPRT), the majority of which have classic Lesch-Nyhan syndrome. Lesch-Nyhan syndrome was described in 1964 as the first disorder of purine metabolism. It is an X-linked disorder characterized by severe neurologic impairment, the development of a compulsive self-destructive behavior, and uric acid nephropathy.