Interpretive Handbook

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.

Due to the various roles these compounds play, the enzymes catalyzing purine and pyrimidine metabolism function as "housekeeping" enzymes. Accordingly, disorders of purine and pyrimidine metabolism can involve all organ systems at any age.

Lesch-Nyhan syndrome (complete deficiency of hypoxanthine-guanine phosphoribosyltransferase) 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.

The diagnosis of the various disorders of purine and pyrimidine metabolism (more than 30 enzyme deficiencies have been described although only 17 are known to cause disease) is based on the clinical presentation of the patient, determination of specific concentration patterns of purine and pyrimidine metabolites, followed by confirmatory enzyme assays and/or molecular genetic testing.

Evaluating patients with symptoms suspicious for disorders of purine and pyrimidine metabolism

Monitoring patients with disorders of purine and pyrimidine metabolism

Laboratory evaluation of primary and secondary hyperuricemias

A positive test result could be due to a genetic or nongenetic condition. Additional confirmatory testing would be required.

Abnormal concentrations of measurable compounds will be reported along with an interpretation. The interpretation of an abnormal metabolite pattern includes an overview of the results and of their significance, a correlation to available clinical information, possible differential diagnosis, recommendations for additional biochemical testing and confirmatory studies (enzyme assay, molecular analysis), name, and phone number of contacts who may provide these studies at the Mayo Clinic or elsewhere, and a phone number of the laboratory directors in case the referring physician has additional questions.

No significant cautionary statements.

URACIL

0-2 years: < or =31 mmol/mol creatinine

3-5 years: < or =30 mmol/mol creatinine

6-11 years: < or =28 mmol/mol creatinine

12-17 years: < or =26 mmol/mol creatinine

> or =18 years: < or =35 mmol/mol creatinine

URIC ACID

0-2 years: < or =2,249 mmol/mol creatinine

3-5 years: < or =1,900 mmol/mol creatinine

6-11 years: < or =1,398 mmol/mol creatinine

12-17 years: < or =698 mmol/mol creatinine

> or =18 years: < or =669 mmol/mol creatinine

HYPOXANTHINE

0-2 years: <53 mmol/mol creatinine

3-5 years: <49 mmol/mol creatinine

6-11 years: <43 mmol/mol creatinine

12-17 years: <36 mmol/mol creatinine

> or =18 years: <40 mmol/mol creatinine

XANTHINE

0-2 years: <49 mmol/mol creatinine

3-5 years: <41 mmol/mol creatinine

6-11 years: <30 mmol/mol creatinine

12-17 years: <16 mmol/mol creatinine

> or =18 years: <51 mmol/mol creatinine

Jurecka A: Inborn errors of purine and pyrimidine metabolism. J Inherit Metab Dis 2009;32:247-263