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J Chemother. 2007 Aug;19(4):455-7.

Acute methotrexate-induced encephalopathy--causal relation to homozygous allelic state for MTR c.2756A>G (D919G)?

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Dept. of Neurology, University Hospital of Bonn, Germany.


Methotrexate (MTX) is widely used in the treatment of hematological diseases. The typical side-effects of high-dose MTX chemotherapy on the CNS range from asymptomatic white matter changes to severe CNS demyelination. MTX neuro - toxicity has been described to be associated with homocysteine and folate levels as well as genetic variants affecting methionine metabolism. Here we describe a case of severe, acute MTX-induced encephalopathy in a patient who was found to be homozygous for the rare missense variant methionine synthase (MTR) c.2756A>G (D919G), which may have modified the effect of MTX on homocysteine metabolism. This finding encourages further studies to determine to what extent the individual conditions of folate and methionine metabolism influence the effects or side-effects of MTX treatment.

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