Successful Azathioprine Treatment with Metabolite Monitoring in a Pediatric Inflammatory Bowel Disease Patient Homozygous for TPMT*3C.
10.3349/ymj.2013.54.6.1545
- Author:
Mi Na LEE
1
;
Hye In WOO
;
Yoo Min LEE
;
Ben KANG
;
Jong Won KIM
;
Yon Ho CHOE
;
Soo Youn LEE
Author Information
1. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. suddenbz@skku.edu
- Publication Type:Case Reports ; Research Support, Non-U.S. Gov't
- Keywords:
Thiopurine methyltransferase;
azathioprine;
inflammatory bowel disease;
metabolite levels
- MeSH:
Adolescent;
Azathioprine/adverse effects/*therapeutic use;
Homozygote;
Humans;
Inflammatory Bowel Diseases/*drug therapy/*enzymology/*genetics/metabolism;
Male;
Methyltransferases/*genetics
- From:Yonsei Medical Journal
2013;54(6):1545-1549
- CountryRepublic of Korea
- Language:English
-
Abstract:
Thiopurine S-methyltransferase (TPMT) methylates purine analogues, showing TPMT activity in inverse relation to concentrations of active metabolites such as 6-thioguanine nucleotide (6-TGN). With conventional dosing of thiopurines, patients with homozygous variant TPMT alleles consistently suffer from severe myelosuppression. Here, we report a patient with TPMT*3C/*3C who managed successfully with monitoring of thiopurine metabolites. The patient was an 18-year-old male diagnosed with Crohn's disease. The standard dose of azathioprine (AZA) (1.8 mg/kg/day) with mesalazine (55.6 mg/kg/day) was prescribed. Two weeks after starting AZA treatment, the patient developed leukopenia. The DNA sequence analysis of TPMT identified a homozygous missense variation (NM_000367.2: c.719A>G; p.Tyr240Cys), TPMT*3C/*3C. He was treated with adjusted doses of azathioprine (0.1-0.2 mg/kg/day) and his metabolites were closely monitored. Leukopenia did not reoccur during the follow-up period of 24 months. To our knowledge, this is the first case of a patient homozygous for TPMT*3C successfully treated with azathioprine in Korea. While a TPMT genotyping test may be helpful to determine a safe starting dose, it may not completely prevent myelosuppression. Monitoring metabolites as well as routine laboratory tests can contribute to assessing drug metabolism and optimizing drug dosing with minimized drug-induced toxicity.
