title: Acute methotrexate-induced encephalopathy--causal relation to homozygous allelic state for MTR c.2756A>G (D919G)?
abstract: 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.
authors.affiliation: Dept. of Neurology, University Hospital of Bonn, Germany. Michael.Linnebank@ukb.uni-bonn.de
authors.forename: M
authors.initials: M
authors.lastname: Linnebank
authors.forename: S
authors.initials: S
authors.lastname: Malessa
authors.forename: S
authors.initials: S
authors.lastname: Moskau
authors.forename: A
authors.initials: A
authors.lastname: Semmler
authors.forename: H
authors.initials: H
authors.lastname: Pels
authors.forename: T
authors.initials: T
authors.lastname: Klockgether
authors.forename: U
authors.initials: U
authors.lastname: Schlegel
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000208:Acute Disease; D000328:Adult; D000483:Alleles; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002051:Burkitt Lymphoma / Q000188:drug therapy; D005260:Female; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D009154:Mutation; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000235:genetics*
chemical_list: D000964:Antimetabolites, Antineoplastic; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D008727:Methotrexate