Folate-induced reversal of leukoencephalopathy and intellectual decline in methylene-tetrahydrofolate reductase deficiency: variable response in siblings

Abstract

Homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency may present with variable neurological manifestations. Radiological features include white matter changes (leukoencephalopathy). Clinical, biochemical, and radiological response to treatment may again be variable. Here we present a 12-year follow-up of two siblings on the same treatment regimen, with contrasting long-term findings. The first patient, a female presenting at 15 years, showed a good clinical response, substantial intellectual gain, and complete reversal of leukoencephalopathy. Her brother presented at 13 years 9 months and showed limited clinical and cognitive improvement with persistence of the leukoencephalopathy. Both siblings showed a partial biochemical response to treatment.

MTHFR 677C>T effects on anterior cingulate structure and function during response monitoring in schizophrenia: a preliminary study

“…The mechanism through with MTHFR may influence white matter integrity in schizophrenia remains uncertain; however, the lack of an interactive effect of MTHFR genotype and FA on error-related dACC activation suggests that the two deficits may be relatively independent sequelae of having the T allele. Interestingly, MTHFR deficiency has been associated with leukoencephalopathy (Bishop et al 2008; Tallur et al 2005; Walk et al 1994), and the 677T allele has been linked to white matter lesions in large cohorts of elderly subjects (Hong et al 2009; Kohara et al 2003). These reports speculate that the observed white matter changes are due to homocysteine elevations, a direct metabolic consequence of low MTHFR activity.…”

Reversible leukoencephalopathy and cerebral atrophy in homocystinuria due to MTHFR deficiency: A treatable metabolic disorder

“…1,2 Reversible leukoencephalopathy has previously been described in patients with classical homocystinuria as well as in MTHFR deficiency. 3,4 Brain white matter changes in hyperhomocysteinemia have been attributed to hypermethionemia in patients with classical homocystinuria and to impaired myelination in remethylation disorders. 3,5 Herein we report reversible leukoencephalopathy and cerebral atrophy in an adolescent with hyperhomocysteinemia due to MTHFR deficiency.…”