Folate transport to the brain depends on
ATP-driven
folate receptor-mediated transport across choroid plexus epithelial cells. Failure of
ATP production in
Kearns-Sayre syndrome syndrome provides one explanation for the finding of low spinal fluid (CSF)
5-methyltetrahydrofolate (5MTHF) levels in this condition. Therefore, we suspect the presence of reduced
folate transport across the blood-spinal fluid barrier in other mitochondrial
encephalopathies. In the present patient with mitochondrial complex I encephalomyopathy a low
5-methyltetrahydrofolate level was found in the CSF. Serum
folate receptor
autoantibodies were negative and could not explain the low spinal fluid
folate levels. The epileptic
seizures did not respond to
primidone monotherapy, but addition of ubiquinone-10 and radical scavengers reduced seizure frequency. Add-on treatment with
folinic acid led to partial clinical improvement including full control of
epilepsy, followed by marked recovery from
demyelination of the brainstem, thalamus, basal ganglia and white matter. Cerebral
folate deficiency is not only present in
Kearns-Sayre syndrome but may also be secondary to the failure of mitochondrial
ATP production in other mitochondrial
encephalopathies. Treatment with
folinic acid in addition to supplementation with radical scavengers and cofactors of deficient respiratory
enzymes can result in partial clinical improvement and reversal of abnormal myelination patterns on neuro-imaging.