Thiopurine S-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. Thiopurine drugs are used to treat some autoimmune disorders, including Crohn's disease and rheumatoid arthritis, which occur when the immune system malfunctions. These drugs are also used to treat several forms of cancer, particularly cancers of blood-forming tissue (leukemias) and cancers of immune system cells (lymphomas). Additionally, thiopurine drugs are used in organ transplant recipients to help prevent the immune system from attacking the transplanted organ.

A potential complication of treatment with thiopurine drugs is damage to the bone marrow (hematopoietic toxicity). Although this complication can occur in anyone who takes these drugs, people with TPMT deficiency are at highest risk. Bone marrow normally makes several types of blood cells, including red blood cells, which carry oxygen; white blood cells, which help protect the body from infection; and platelets, which are involved in blood clotting. Damage to the bone marrow results in myelosuppression, a condition in which the bone marrow is unable to make enough of these cells. A shortage of red blood cells (anemia) can cause pale skin (pallor), weakness, shortness of breath, and extreme tiredness (fatigue). Low numbers of white blood cells (neutropenia) can lead to frequent and potentially life-threatening infections. A shortage of platelets (thrombocytopenia) can cause easy bruising and bleeding.

Many healthcare providers recommend that patients' TPMT activity levels be tested before thiopurine drugs are prescribed. In people who are found to have reduced enzyme activity, the drugs may be given at a significantly lower dose or different medications can be used to reduce the risk of hematopoietic toxicity.

TPMT deficiency does not appear to cause any health problems other than those associated with thiopurine drug treatment.