Posterior-predominant leukoencephalopathy which was caused by methylenetetrahydrofolate reductase deficiency and successfully treated with folic acid

Abstract

A 35-year-old woman was admitted with subacute intellectual deterioration. Laboratory studies showed elevated total homocysteine and decreased folic acid. MRI revealed leukoencephalopathy with a posterior predominance, and hyperintensity in the pyramidal tracts on T2-weighted and FLAIR images. The enzyme assay showed a deficiency of methylenetetrahydrofolate reductase (MTHFR) activity with low residual activity of 4.2% of the mean control value in cultured fibroblasts. Sequence analysis of the MTHFR gene demonstrated two homozygous missense mutations, c.677C>T (p.Ala222Val) and c.685A>C (p.Ile225Leu). c.677C>T (p.Ala222Val) is known as a common polymorphism and c.685A>C (p.Ile225Leu) is considered to be a novel polymorphism. A diagnosis of MTHFR deficiency was made. Treatment with folic acid, vitamin B12 and B6 made significant improvement of intellectual deterioration and reduction in the total homocysteine level. They also made marked resolution of leukoencephalopathy. Posterior-predominant leukoencephalopathy was found to be an excellent marker of MTHFR deficiency, and may help to establish the diagnosis.