What is thiopurine methyltransferase deficiency?
What is thiopurine methyltransferase deficiency?
Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body’s immune system.
What is thiopurine methyltransferase test?
Thiopurine Methyltransferase, RBC. Phenotype test that assesses risk for severe bone marrow toxicity with standard dosing of thiopurine drugs. Performed before thiopurine therapy is initiated.
What are thiopurines used for?
Thiopurine drug therapy is used for autoimmune diseases, inflammatory bowel disease, acute lymphoblastic leukemia, and to prevent rejection after solid organ transplant. The inactivation of thiopurine drugs is catalyzed in part by thiopurine methyltrasferase (TPMT) and nudix hydrolase 15 (NUDT15).
Where is the TPMT gene?
The human TPMT gene is 34 kb in length, consists of 10 exons, maps to chromosome 6p22. 3 [14] and has a pseudo-gene located on chromosome 18 [15]. Twenty-eight variant alleles have been identified [16], most of which have been associated with decreased activity in vitro [17].
What is thiopurine methyltransferase RBC?
Thiopurine methyltransferase (TPMT) is an enzyme that breaks down (metabolizes) a class of drugs called thiopurines. These drugs are used to suppress the immune system and are prescribed to treat various immune-related conditions or blood disorders (e.g., leukemia).
Is thioguanine an immunosuppressant?
Azathioprine, 6-mercaptopurine, and 6-thioguanine are immunosuppressive drugs indicated in the prevention of graft rejection, and treatment of auto-immune disease or inflammatory bowel disease. Their anti-nucleotidic properties are also used for the treatment of acute leukaemia.
What is the mechanism of action of azathioprine?
Mechanism of action Azathioprine inhibits purine synthesis. Purines are needed to produce DNA and RNA. By inhibiting purine synthesis, less DNA and RNA are produced for the synthesis of white blood cells, thus causing immunosuppression.
How do thiopurines treat IBD?
Activation of the mucosal immune system has been found to play a key role, specifically in the chronic phase of this disease. The thiopurines are immunosuppressive drugs, deactivating key processes in T lymphocytes that lead to inflammation.
What is a thiopurine drug?
The thiopurine drugs are purine antimetabolites widely used in the treatment of acute lymphoblastic leukemia, autoimmune disorders (e.g., Crohn’s disease, rheumatoid arthritis), and organ transplant recipients. Metabolism is catalyzed by S-methyltransferase.
How does the TPMT enzyme affect a azathioprine drug?
Patients with TPMT deficiency treated with standard doses of azathioprine or 6-mercaptopurine are at significantly increased risk of myelosuppression, bleeding, infection, and death associated with increased levels of cytotoxic 6-thioguanine nucleotide levels in the red blood cells.
What is thioguanine nucleotide?
Abstract. Background: Thioguanine nucleotides (TGNs) are the active product of thiopurine metabolism. Levels have been correlated with effective clinical response. Nonetheless, the value of TGN monitoring in clinical practice is debated.
Does thioguanine cause diarrhea?
SIDE EFFECTS: Upset stomach, nausea, vomiting, and diarrhea may occur. If any of these effects persist or worsen, contact your doctor or pharmacist promptly. Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects.
