Thiopurine methyltransferase

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.