|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;
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
|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|