A 19-year-old university student with no personal or family history of neurologic disorders developed convulsions and was administered phenytoin. Two months later, he developed lower limb-dominant acute demyelinating polyneuropathy, from which he recovered within 2 months. At age 20, he rapidly developed visual disturbances and paraplegia from phenytoin intoxication. Cranial magnetic resonance imaging (MRI) revealed leukoencephalopathy with no evidence of thrombosis or vasoconstriction. Hyperhomocysteinemia, hypomethioninemia, low serum folate concentration, and an absence of megaloblastic anemia were consistent with the diagnosis of methylenetetrahydrofolate reductase (MTHFR) deficiency. A genomic DNA sequence analysis demonstrated compound heterozygosity for two missense mutations in the MTHFR gene, namely, [458G>T + 459C>T] (Gly149Val) and 358G>A (Ala116Thr), both of which are known pathogenic mutations. An absence of leukoencephalopathic changes on MRI scans performed 9 months previously strongly suggested that phenytoin intoxication caused acute leukoencephalopathy. Therefore, phenytoin may be an aggravating factor of remethylation defects in patients with MTHFR deficiency.
Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.