Successful azathioprine treatment with metabolite monitoring in a pediatric inflammatory bowel disease patient homozygous for TPMT3C

• Published in: Yonsei medical journal 2013, 54(6), , pp.1545-1549
• Main Authors: Lee, Mi-Na, Woo, Hye In, Lee, Yoo Min, Kang, Ben, Kim, Jong-Won, Choe, Yon Ho, Lee, Soo-Youn
• Format: Article
• Language: English
• Subjects: Adolescent; Azathioprine - adverse effects; Azathioprine - therapeutic use; Case Report; Homozygote; Humans; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - enzymology; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - metabolism; Male; Methyltransferases - genetics; 의학일반
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2013.54.6.1545

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.