Thiopurine methyltransferase - red cells

Last updated: Tuesday, 30, March, 2004

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Item Process
Specimen

5 mL blood in lithium heparin or EDTA tube.

Method

Radiometric enzyme assay.

Reference Interval

Check with laboratory. Typically, 0.5-0.9 U/g Hb.

Application

Identification of patients at risk of potentially fatal myelosuppression from usual doses of thiopurines (eg, azathioprine, 6-mercaptopurine, thioguanine). 

All patients should be assessed prior to commencement of the drug, not retrospectively to ascertain the cause of an adverse reaction.

Interpretation

Approximately 0.3% of the population has a profound genetic deficiency of thiopurine methyltransferase, the major route for detoxification of thiopurines used in immunosuppression and oncology.
These patients develop severe marrow suppression if given usual doses of a thiopurine drug or prodrug. The condition is inherited as an autosomal recessive trait, and about 11% of the population are carriers.
Carriers may also show decreased tolerance to the drugs, although not as severely as the severely deficient patients.

Reference

Krynetski EY. Pharmacogenetics 1996; 6: 279-290.