Clinical Use: Detection of individuals with low thiopurine methyltransferase activity who are at risk for excessive myelosuppression or severe hematopoietic toxicity when taking azathioprine or 6-MP.
Background: Thiopurine methyltransferase (TPMT) deficiency is a condition in which patients treated with standard doses of the immunosuppressant azathioprine or the antineoplastic drug 6-mercaptopurine (6-MP) may develop life-threatening myelosuppression or severe hematopoietic toxicity. The metabolic conversion of azathioprine or 6-MP to purine nucleotides and the subsequent incorporation of these nucleotides into DNA plays 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 levels antimetabolite 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 are heterozygous carriers of TPMT mutations. Adverse effects of azathioprine 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 azathioprine or 6-MP is important for purposes of calculating drug dosages.

Reference Ranges: Normal: 68 – 150 mU/L
Low: 20 – 67 mU/L
High: >150 mU/L
Associated Diseases:
Patient Preparation: None required
Specimen Requirements: Blood specimen in an EDTA (purple top) tube
Turnaround Time: 1 week
Additional Information: Recent blood transfusions may mask a deficient TPMT result.
Referred Test: Referred Test
Location: City Hospital