Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xanthine oxidase deficiency was identified in a 16-year-old girl with acute lymphocytic leukemia (ALL). Despite the enzyme deficiency, the patient tolerated high doses of 6-mercaptopurine (6-MP), a drug which is normally inactivated by the action of xanthine oxidase. This rate clinical situation may be analogous in the practice to that of the patient receiving 6-MP who is also given allopurinol, which inhibits xanthine oxidase activity. The implications of these observations on the determination of appropriate drug dosages for patients receiving these two agents are discussed.
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PMID:Acute lymphocytic leukemia in a child with congenital xanthine oxidase deficiency: implications for therapy. 694 80

Azathioprine is an immunosuppressor used with ciclosporin and corticosteroids after organ transplantation. Azathioprine is rapidly transformed into 6-mercaptopurine which in turn is metabolized by three competitive pathways: a) intracellular hypoxanthine guanine phosphoribosyl transferase leads to 6-thioguanine nucleotides which can damage chromosome DNA; b) thiopurine methyltransferase produces inactive methylated derivatives; c) xanthine oxidase produces thiouric acid. Due to inter-individual variations in the later two pathways, azathioprine dose must be adapted to each patient. A 48-year-old female patient underwent renal transplantation in 1994 and was given immunosuppressive therapy combining thymoglobulins, azathioprine and ciclosporin. Severe leukopenia (< 3000/mm3) occurred on day 5 requiring withdrawal of azathioprine. Known hypouricaemia (< 50 mumol/l) suggested xanthine oxidase deficiency. Laboratory results confirmed xanthine oxidase deficiency and also revealed reduced thiopurine methyltransferase activity (14.9 pmol/h/mg Hb). Azathioprine toxicity was confirmed by regression of the leukopenia after withdrawal and recurrence at rechallenge. Xanthine oxidase deficiency occurs in 2% of the general population. Reduced thiopurine methyltransferase activity affects 11% of the population. The combined presence of these two genetic anomalies led to early and sudden intolerance to azathioprine and emphasize the need to develop new immunosuppressor agents degraded by other metabolic pathways.
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PMID:[Hematotoxicity caused by azathioprine genetically determined and aggravated by xanthine oxidase deficiency in a patient following renal transplantation]. 766 22