TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: PUPYU    
Purines and Pyrimidines Panel, Urine

Useful For Suggests clinical disorders or settings where the test may be helpful

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

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

At least 35 known inherited disorders of purine and pyrimidine metabolism exist representing a diversity of neurological, immunological, hematological, and renal manifestations.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 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.

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.

Purines and pyrimidines panel

reference values

(all results reported as mmol/mol creatinine)

Age range 

0-3 years

4-6 years

7-12 years

13-18 years

>18 years

Uracil

< or =50

< or =30

< or =25

< or =20

< or =20

Thymine

< or =3

< or =3

< or =3

< or =3

< or =3

Adenine

< or =3

< or =3

< or =3

< or =3

< or =3

Hypoxanthine

< or =65

< or =30

< or =30

< or =30

< or =30

Xanthine

< or =54

< or =21

< or =35

< or =15

< or =20

Orotic

< or =4

< or =4

< or =3

< or =3

< or =5

Dihydroorotic Acid

< or =3

< or =3

< or =3

< or =3

< or =3

Uric Acid

350-2500

200-2000

200-1400

150-700

70-700

Deoxythymidine

< or =3

< or =3

< or =3

< or =3

< or =3

Deoxyuridine

< or =3

< or =3

< or =3

< or =3

< or =3

Thymidine

< or =3

< or =3

< or =3

< or =3

< or =3

Uridine

< or =10

< or =3

< or =3

< or =3

< or =3

Deoxyadenosine

< or =3

< or =3

< or =3

< or =3

< or =3

Deoxyinosine

< or =3

< or =3

< or =3

< or =3

< or =3

Deoxyguanosine

< or =3

< or =3

< or =3

< or =3

< or =3

Adenosine

< or =3

< or =3

< or =3

< or =3

< or =3

Inosine

< or =6

< or =3

< or =3

< or =3

< or =3

Guanosine

< or =4

< or =3

< or =3

< or =3

< or =3

5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR)

< or =3

< or =3

< or =3

< or =3

< or =3

Succinyladenosine

< or =16

< or =3

< or =3

< or =3

< or =3

S-Sulfocysteine

< or =11

< or =5

< or =5

< or =5

< or =5

Dihydrouracil

< or =15

< or =6

< or =6

< or =6

< or =6

Dihydrothymine

< or =11

< or =3

< or =3

< or =3

< or =3

N-carbamoyl-B-alanine

< or =30

< or =10

< or =10

< or =10

< or =10

N-carbamoyl-B-aminoisobutyric
Acid

< or =20

< or =3

< or =3

< or =3

< or =3

Interpretation Provides information to assist in interpretation of the test results

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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Jinnah HA, Friedmann T: Lesch-Nyhan disease and its variants. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed November 23, 2020. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225089443

2. Balasubramaniam S, Duley JA, Christodoulou J: Inborn errors of purine metabolism: clinical update and therapies. J Inherit Metab Dis. 2014 Sep;37(5):669-686

3. Balasubramaniam S, Duley JA, Christodoulou J: Inborn errors of pyrimidine metabolism: clinical update and therapy. J Inherit Metab Dis. 2014 Sep;37(5):687-698