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ID:301 Thiopurine Methyl Transferase (TPMT)
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DescriptionThis enzyme controls the rate of metabolism of thiopurine drugs. TPMT activity should be determined before starting therapy, however, the test can be performed if patient is already on treatment. Repeat requests for TPMT are not usually indicated and repeat samples will be rejected unless discussed with the laboratory first.
IndicationUsed as a predictive test for azothioprine sensitivity.
Additional InfoThiopurine drugs (azothioprine and 6-mercaptopurine) are converted in vivo to cytotoxic thionucleotides which cause white cell supression. The enzyme TPMT provides a major catabolic pathway for these drugs. In the absence of TPMT there will an over dose effect - resulting in complete bone marrow supression. 1 in 300 caucasians has complete deficiency of TPMT which results in absolute intolerance to azothioprine. A partial deficiency of TPMT occurs in 1 in 10 of the population and these patients are at high risk (>60%) from azothioprine intolerance. Although patients on azothioprine have FBC monitored regularly it is useful to assess their TPMT status prior to the initiation of therapy. Another group of patients exist who have normal erythrocyte TPMT activity but still display sensitivity to azothiporine. The majority of these are probably intolerant to imidazole (azothioprine is actually a pro-drug for 6-mercaptopurine which is released in the gut when the imidazole moiety is cleaved from azothioprine). The rest of these patients may be intolerant to azothiporine despite normal activity of TPMT due to counter-indicated drugs (e.g Allopurinol), inherited xanthine oxidase deficiency (exclude by confirming normal plasma uric acid), intercurrent viral infection, deficiency of purine 5-nucleotidase.
Concurrent Testsna
Dietary Requirementsna

InterpretationNormal TPMT activity indicates the chance of bone marrow supression on a normal azothioprine dose is very low. Patients with reduced activity of TPMT should be started on a reduced dose. Patients with very high activity of TPMT may require higher doses. Low TPMT activity in samples >8 days old should be interpreted with caution.

Ref. Range (Male)See note
Ref. Range (Female)
Ref. Range (Paed)
Ref. Range NotesDeficient <10, Low 20-67, Normal 68-150, High >150 mU/L

IP Acute TAT7 days
IP Routine TAT7 days
GP Acute TAT7 days
GP Routine TAT7 days
Turnround CommentJenna
Originally edited by : DT. Last edited on 10/08/2019 15:48:55. Published By sylvia bennett on 10/08/2018 15:48:55.