What is known and objective: Thiopurine methyltransferase (TPMT) enzyme is an important component in the metabolism of azathioprine (AZA). Its mutation may lead to AZA-induced toxicity. The dysfunctional genetic variant TPMT *3C is of low frequency among Asians. Moreover, AZA-induced toxicity still occurs in some patients with normal TPMT activity. This suggests that additional factors, including other genetic variants, may contribute to such toxicity. Recent studies described a strong association between a variant of the NUDT15, a gene that mediates the hydrolysis of some nucleoside diphosphate derivatives, and thiopurine-related myelosuppression in Asians. We report the first case of a Chinese patient with AZA-induced severe toxicity with no clinically significant TPMT variant but with the NUDT15 c.415C>T allele.
Case summary: A 40-year-old Chinese patient with PBC-AIH overlap syndrome had been receiving for one month, azathioprine (50 mg/day) and methylprednisolone (24 mg/day) based on his TPMT*3C wild-type genotype. The patient developed serious myelosuppression and hair loss. AZA was stopped, and the patient was given liver-protective drugs and supportive treatment. TPMT and NUDT15 gene sequencing suggests that NUDT15 c.415C>T mutation was the likely cause of the adverse reaction.
What is new and conclusion: NUDT15 c.415C>T may be another predictor of AZA-induced leukocytopenia. If further well-controlled studies validate this association with sufficient predictive power, NUDT15 and TPMT genotyping before starting AZA treatment may become appropriate.
Keywords: NUDT15 c.415C>T; azathioprine; hair loss; myelosuppression; thiopurine methyltransferase.
© 2016 John Wiley & Sons Ltd.