Mercaptopurine
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Mercaptopurine Leukopenia: case report
A 20-year-old woman developed leukopenia during treatment with mercaptopurine for ulcerative colitis (UC). The woman, who was diagnosed with UC, started receiving mesalazine. However, she developed tachycardia [unknown aetiology], and her mesalazine was discontinued. Subsequently, she started receiving prednisolone and mercaptopurine [6-mercaptopurine]. However, she developed mercaptopurine-treatment related leukopenia [duration of treatment to reaction onset and outcome not stated]. Thus, the woman’s mercaptopurine and prednisolone treatment was discontinued. Thereafter, thiopurine methyltransferase (TPMT; it ensures the degradation and efficacy of azathioprine) genotyping was performed by Sanger sequencing. The results of the TPMT genotyping were available after she had received azathioprine. Genotyping of TPMT revealed no mutations in *2, *3A and *3C. A novel class 5 deleterious mutation (c.483_484del, p.Asp162Serfs * 26) was detected in exon 7. This deletion is involved in a shift in the reading frame of the sequence, and it induces STOP codon at position 188 of the amino acids (Tyrosine→Stop) in the middle of the exon 8. This molecular alteration leads to generation of truncated TPMT protein without exon 9 and exon 10. In addition, this leads to appearance of TPMT * 16 "hot spot", inducing a mutation in one of the alleles. Thereafter, she was received first-line anti–TNF-biotherapy with adalimumab, following which a transient improvement was noted. But, her symptomatology reoccurred. Thereafter, she received vedolizumab, and then therapeutic exhaustion was observed. Then, she received treatment with golimumab, with partial improvement. Eventually, she was started on ustekinumab, following which improvement was observed. But, after 3 months, her UC reoccurred with a weight loss (of 6kg) and in the form of severe acute colic. As her UC was not under control, azathioprine was reintroduced at reduced dose due to the mutation in the TPMT gene. Despite treatment with azathioprine and infliximab, disease progression was observed. Hence, she was started on new therapy with tofacitinib. Harmand P-O, et al. Thiopurine drugs in the treatment of ulcerative colitis: Identification of a novel deleterious mutation in tpmt. Genes 11: 1-14, No. 10, Oct 2020
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Reactions 14 Nov 2020 No. 1830
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