Journal
JOURNAL OF CHEMOTHERAPY
Volume 19, Issue 4, Pages 455-457Publisher
ESIFT SRL
DOI: 10.1179/joc.2007.19.4.455
Keywords
methotrexate; 5-methyltetrahydrofolate-homocysteine s-methyltransferase; methionine synthase; pollymorphism; genetic; encephalopathy; metabolic; chemotherapy; methionine; folic acid
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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 neurotoxicity has been described to be associated with homocysteline 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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