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Arthritis Rheum. 1997 Oct;40(10):1896-8.

Azathioprine-induced severe pancytopenia due to a homozygous two-point mutation of the thiopurine methyltransferase gene in a patient with juvenile HLA-B27-associated spondylarthritis.

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Children's Hospital of University Erlangen-Nürnberg, Erlangen, Germany.


Severe pancytopenia due to azathioprine (AZA) toxicity in patients with autoimmune diseases is not uncommon. We describe a 14-year-old girl with HLA-B27+ spondylarthritis who was treated with AZA 3 mg/kg/day and who suddenly developed severe pancytopenia in the seventh week of treatment. Analysis of the catabolic pathway of AZA revealed a homozygous deficiency of thiopurine methyltransferase (TPMT) on the basis of a combined 2-point mutation at nucleotide positions 460 and 719 in the gene for TPMT, causing a toxic level of the metabolic active 6-thioguanine nucleotides (6-TGN) (2,394 pmoles/8 x 10(8) red blood cells). The patient was transfusion dependent and finally recovered 8 weeks after the development of the pancytopenia. At that time, 6-TGN had already returned to normal therapeutic levels. Family studies revealed another homozygous deficiency in the mother, while the other family members were heterozygous.

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