Thiopurine S methyltranferase deficiency
Overview
Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme (EC 2.1.1.67) that methylates thiopurine compounds. The methyl donor is S-adenosyl-L-methionine, which is converted to S-adenosyl-L-homocysteine. This gene encodes the enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents. Genetic polymorphisms that affect this enzymatic activity are correlated with variations in sensitivity and toxicity to such drugs within individuals. A pseudogene for this locus is located on chromosome 18q
Symptoms
* Reduced blood production by the bone marrow * Low TPMT activity * Blood toxicity * Liver toxicity * Fever
Diagnosis
Measurement of TPMT activity is encouraged prior to commencing the treatment of patients with thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine.; as patients with low activity (10% prevalence) or especially absent activity (prevalence 0.3%) are at a heightened risk of drug-induced bone marrow toxicity due to accumulation of the unmetabolised drug. Reuther et al found that about 5% of all thiopurine therapies will fail due to toxicity. This intolerant group could be anticipated by routine measurement of TPMT activity. There appears to be a great deal of variation in TPMT mutation, with ethnic differences in mutation types accounting for variable responses to 6MP.
Treatment
* Urinary & Bladder Specialists (Urology): o Urology o Urological Surgery * Kidney Health Specialists (Nephrology): o Nephrology (Kidney Health) o Pediatric Nephrology (Child Kidney Health) o Urology (Urinary/Bladder)