Thiopurine Methyltransferase (TPMT), Erythrocytes
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Detection of individuals with low thiopurine methyltransferase activity who are at risk for excessive myelosuppression or severe hematopoietic toxicity when taking azathioprine (Imuran) or 6-mercaptopurine (Purinethol)
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Enzymatic End point/Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Thiopurine Methyltransferase, RBC
TPMT (Thiopurine Methyltransferase)
TPMT (Thiopurine Methyltransferase)
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Preferred: Green top (sodium heparin)
Acceptable: EDTA or lithium heparin
Specimen Volume: 5 mL
1. 1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
2. 2. If not ordering electronically, submit a Biochemical Genetics Request Form (Supply T439) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross reject
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole blood||Refrigerated||6 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Thiopurine methyltransferase (TPMT) deficiency is a condition in which patients treated with standard doses of the immunosuppressant azathioprine (AZA, Imuran) or the antineoplastic drug 6-mercaptopurine (6-MP, Purinethol) may develop life-threatening myelosuppression or severe hematopoietic toxicity. The metabolic conversion of AZA or 6-MP to purine nucleotides and the subsequent incorporation of these nucleotides into DNA play an important role in both the therapeutic efficacy and the toxicity of these drugs. A competitive catabolic route for the metabolism of thiopurines is catalyzed by the TPMT enzyme, which inactivates them by thiomethylation. A balance must be established between these competing metabolic pathways so that: 1) sufficient amounts of drug are converted to the nucleotide to act as an antimetabolite and 2) the antimetabolite levels do not become so high as to cause potentially lethal bone marrow suppression.
TPMT deficiency is an autosomal recessive condition with an incidence of approximately 1 in 300 individuals homozygous for deleterious mutations in the TPMT gene; about 10% of the population is heterozygous carriers of TPMT mutations. The incidence of individuals who are homozygous or heterozygous carriers of TPMT mutations varies by population. Adverse effects of AZA or 6-MP administration can be observed in individuals who are either homozygous or heterozygous for TPMT deficiency. As such, knowing a patient's TPMT status prior to treatment with AZA or 6-MP is important for purposes of calculating drug dosages.
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.
> or =15.0 U/mL RBC (normal)
10.1-14.9 U/mL RBC (low normal)
6.0-10.0 U/mL RBC (carrier)
0.0-5.9 U/mL RBC (deficient)
Reference values apply to all ages.
Expected values for individuals in the carrier range for thiopurine methyltransferase (TPMT) deficiency are between 6.0 and 10.0 U/mL RBC.
Expected values for individuals homozygous for deleterious mutations in the TPMT gene (deficient TPMT) are < or =5.9 U/mL RBC.
Results between 10.1 and 14.9 U/mL RBC represents probable low normal.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
There is partial overlap for the distribution of thiopurine methyltransferase activities observed between patients with normal and heterozygous genotypes; thus, results that fall within the low-normal range can occur because of assay variability or biological variation.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1.Relling MV, Gardner EE, Sandborn WJ, et al: Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther 2011;89(3):387-391
2. Sandborn WJ: Pharmacogenomics and IBD: TPMT and thiopurines. Inflamm Bowel Dis 2004;10:Suppl 1 S35-S37
3. Schedel J, Godde A, Schutz E, et al: Impact of thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations in patients with chronic inflammatory diseases. Ann N Y Acad Sci 2006;1069:477-491
4. Zhou S: Clinical pharmacogenomics of thiopurine S-methyltransferase. Curr Clin Pharmacol 2006;1:119-128
Method Description Describes how the test is performed and provides a method-specific reference
Thiopurine methyltransferase (TPMT) catalyzes the metabolism of 6-mercaptopurine to 6-methylmercaptopurine (6-MMP) in erythrocytes, utilizing S-adenosyl-L-methionine as the methyl group. The rate of formation of 6-MMP is an indication of the amount of TPMT present in a patient's red blood cell lysate. Reactions that would interfere with the specific TPMT methylation, such as nonenzymatic methylation of 6-MMP and the formation of methylthiopurines other than 6-MMP, are eliminated: Km (Michaelis constant)-appropriate substrate concentrations are employed in a batched reagent to reduce nonenzymatic methylation. Phosphate buffers are used because other buffers allow for the formation of methylthiopurines other than 6-MMP.(Lacey JM, Magera MJ, Matern D, O'Brien JF: Quantitation of 6-methylmercaptopurine for the determination of thiopurine methyltransferase; unpublished Mayo manuscript)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday, Wednesday through Friday; Varies
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
4 days (not reported on Saturday or Sunday)
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Processed specimen stored 1 month
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|80291||Thiopurine Methyltransferase, RBC||21563-2|