26424 Purines and Pyrimidines Panel, Urine (PUPYU)

Adenine, Adenosine, Deoxyadenosine, Deoxyguanosine, Deoxyinosine, Guanosine, Hyperuricemias, Hypoxanthine, Inosine, Orotic Acid, Pyrimidine, Succinyladenosine, Thymidine, Uracil, Thymine, Uric Acid, Uridine, Xanthine, S-Sulfocysteine, Adenine phosphoribosyltransferase deficiency, Adenosine deaminase deficiency, Adenosine monophosphate deaminase deficiency, Adenylosuccinate lyase deficiency, AICAr transformylase/imp cyclohydrolase deficiency, Beta-ureidopropionase deficiency, Carbamoyl phosphate synthetase deficiency, Deoxyguanosine kinase deficiency, Dihydropyrimidinase deficiency, Dihydropyrimidine dehydrogenase deficiency, Hyperornithinemia-hyperammonemia-homocitrullinuria, Lesch-Nyhan syndrome, Molybdenum cofactor deficiency, Phosphoribosyl pyrophosphate synthetase deficiency, Primary hyperoxaluria, Purine metabolism disorders, Purine nucleoside phosphorylase deficiency, Pyrimidine metabolism disorders, Secondary hyperuricemia, Sulfite oxidase deficiency, Thymidine phosphorylase deficiency, Uridine monophosphate synthetase deficiency, Xanthine dehydrogenase and xanthine aldehyde oxidase dual deficiency, Xanthine dehydrogenase deficiency, Xanthine dehydrogenase/xanthine aldehyde oxidase/sulfite oxidase combined deficiency

​Uracil, Thymine, Adenine, Hypoxanthine, Xanthine, Orotic, Dihydroorotic Acid, Uric Acid, Deoxythymidine, Deoxyuridine, Thymidine, Uridine, Deoxyadenosine, Deoxyinosine, Deoxyguanosine, Adenosine, Inosine, Guanoasine, 5-Aminoimidazole-4-carboxyamide 1-beta-D-ribofuranoside (AICAR), Succinyladenosine, S-Sulfocysteine, Dihydrouracil, Dihydrothymine, N-carbomoyl-B-alanine, N-carbomoyl-B-aminoisobutyric Acid

​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

This is recommended screening test for the initial workup of a suspected disorder of purine and pyrimidine metabolism, particularly when clinical features are nonspecific, and includes measurement of purines, pyrimidines, uric acid, and S-sulfocysteine. If the clinical features are suggestive of molybdenum cofactor deficiency, isolated sulfite oxidase deficiency, and hereditary xanthinuria, order SSCTU / S-Sulfocysteine Panel, Urine.

​Patient's age is required.  Collect a random urine specimen.

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

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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 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 molecular genetic testing.

Numerous inborn errors of purine and pyrimidine metabolism have been documented. Clinical features are dependent upon the specific disorder but represent a broad spectrum of manifestations that may include immunodeficiency, developmental delay, nephropathy, and neurologic involvement. The most commonly described disorder of purine metabolism involves a deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) which causes 3 overlapping clinical syndromes depending on the amount of residual enzyme activity. The majority of patients with HPRT deficiency have classic Lesch-Nyhan syndrome, a severe X-linked disorder characterized by crystals in urine, neurologic impairment, mild to severe intellectual disability, development of self-injurious behavior, and uric acid nephropathy.

Treatments for Lesch-Nyhan syndrome include allopurinol, urine alkalinization and hydration for nephropathy, and supportive management of neurologic symptoms. For milder forms of HPRT deficiency, treatment that can mitigate the potentially devastating effects of these diseases are disorder dependent; therefore, early recognition through screening and subsequent confirmatory testing is highly desirable.

Urine S-sulfocysteine is elevated in 2 disorders with similar clinical phenotypes: molybdenum cofactor deficiency (MoCD) and isolated sulfite oxidase deficiency. Molybdenum is an important trace element that is biosynthesized into an important cofactor, which is essential for the proper functioning of the enzymes, xanthine oxidase, sulfite oxidase, and aldehyde oxidase, in addition to nitrogenases and nitrate reductase. Four genes are important in mediating the biosynthetic pathway to create molybdenum cofactor: MOCS1, MOCS2, MOCS3, and GPHN (gephyrin). The 3 clinical types of MoCD are autosomal recessive diseases resulting from 2 pathogenic variants in the respective causative gene. MoCDs result in a progressive neurodegenerative disease that manifests with seizures and brain abnormalities in the first weeks to months of life. The most common type of MoCD is MoCD A, caused by variants in MOCS1 and resulting in neonatal or infantile onset seizures and postnatal encephalopathy with rapidly progressive neurodegeneration. Infants with MoCD B (MOCS2 or MOCS3), and C (GPHN) have all been reported but are rare. Infants with MoCD have increased S-sulfocysteine and hypoxanthine and decreased uric acid concentrations in urine. Treatment for MoCD A only is available via clinical trial with cyclic pyranopterin monophosphate infusion and is most effective when initiated early.

Isolated sulfite oxidase deficiency (ISOD) is an autosomal recessive disorder caused by deficiency of the enzyme sulfite oxidase, which results in progressive neurodegenerative disease in most cases. ISOD is the result of pathogenic variants in the SUOX gene. ISOD is a spectrum of disease ranging from severe, early onset disease that appears in the first days of life with seizures, feeding issues, and neurologic issues causing abnormal muscle tone, to mild, later onset disease manifesting after 6 months of age with developmental delay or regression, movement issues, which can be episodic, and ectopia lentis in some cases. Infants with ISOD have increased S-sulfocysteine and normal hypoxanthine concentrations in urine. Treatment is largely symptomatic, with medication for seizures and movement/neurologic issues. Unfortunately, no treatment for the underlying metabolic defect is currently available. Prevalence is unknown, but ISOD is likely underdiagnosed.

Hereditary xanthinuria results in renal stones and, less commonly, muscle pain and cramping caused by accumulation of xanthine that forms crystals in the kidneys and muscle tissue. There are 2 types of hereditary xanthinuria: type I caused by deficiency of xanthine dehydrogenase resulting from pathogenic variants in the XDH gene, and type II caused by deficiency of molybdenum cofactor sulfurase resulting from variants in the MOCOS gene. Individuals with xanthinuria have increased xanthine and decreased uric acid concentrations in urine. The incidence of both types of hereditary xanthinuria is about 1 in 69,000 individuals.

​Additional confirmatory testing via enzyme assays and molecular genetic testing is required for follow-up of abnormal results.

Reference Values

Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

​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, and a phone number of the laboratory directors in case the referring physician has additional questions.