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

M Linnebank1, S Malessa, S Moskau

  • 1Dept. of Neurology, University Hospital of Bonn, Germany. Michael.Linnebank@ukb.uni-bonn.de

Journal of Chemotherapy (Florence, Italy)
|September 15, 2007
PubMed

Insights

Methotrexate (MTX) chemotherapy can cause CNS side effects. A patient with a rare MTR gene variant experienced severe MTX encephalopathy, suggesting a link between genetic factors and MTX neurotoxicity.

Area of Science:

  • Neuroscience
  • Pharmacogenomics
  • Oncology

Background:

  • Methotrexate (MTX) is a key chemotherapy agent for hematological malignancies.
  • High-dose MTX can lead to central nervous system (CNS) toxicity, including demyelination.
  • MTX neurotoxicity is potentially linked to homocysteine, folate metabolism, and genetic factors.

Purpose of the Study:

  • To report a case of severe MTX-induced encephalopathy.
  • To investigate the role of genetic variants in MTX neurotoxicity.

Main Methods:

  • Case report of a patient treated with high-dose MTX.
  • Genetic analysis to identify variants in methionine metabolism pathways.

Main Results:

  • The patient presented with severe, acute MTX encephalopathy.
  • The patient was homozygous for the MTR c.2756A>G (D919G) missense variant.
  • This variant may influence homocysteine metabolism and MTX effects.

Conclusions:

  • The MTR c.2756A>G variant may predispose individuals to severe MTX neurotoxicity.
  • Individual folate and methionine metabolism influence MTX treatment outcomes.
  • Further research is needed to elucidate the pharmacogenomic impact of MTX.

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