title: Should we test TPMT enzyme levels before starting azathioprine?
abstract: Thiopurine methyltransferase (TPMT) is the main enzyme responsible for inactivating toxic products of azathioprine (AZA) metabolism. Patients with homozygous deficiency of this enzyme have no enzyme activity and ideally should not be given AZA. Patients with heterozygous deficiency have 50% of enzyme activity and have been shown to respond well and tolerate half a standard dose. We describe a patient with homozygous deficiency of TPMT who developed life threatening neutropenic sepsis, and advocate that all patients should be tested for TPMT activity prior to starting AZA therapy.
authors.affiliation: Department of Haematology, Singleton Hospital, Swansea, UK.
authors.forename: Vijay Samuel
authors.initials: VS
authors.lastname: Richard
authors.forename: Deana
authors.initials: D
authors.lastname: Al-Ismail
authors.forename: Ahmed
authors.initials: A
authors.lastname: Salamat
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001379:Azathioprine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000473:pathology; D003955:Diagnostic Tests, Routine / Q000191:economics / Q000706:statistics & numerical data; D005260:Female; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008658:Inactivation, Metabolic; D015122:Mercaptopurine / Q000493:pharmacokinetics; D008745:Methylation; D008780:Methyltransferases / Q000097:blood* / Q000172:deficiency; D009503:Neutropenia / Q000139:chemically induced* / Q000150:complications; D011355:Prodrugs / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018805:Sepsis / Q000209:etiology*; D006113:United Kingdom
chemical_list: D007166:Immunosuppressive Agents; D011355:Prodrugs; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine