Kearns-sayre syndrome with reduced plasma and cerebrospinal fluid folate

A young woman with Kearns-Sayre syndrome and progressive central nervous system deterioration over 15 years had decreased plasma and cerebrospinal fluid folate levels while receiving phenytoin for a seizure disorder. A muscle biopsy showed a “ragged red fiber” myopathy with reduced muscle carnitine and mitochondrial enzymes. Computed tomographic brain scans showed cerebral white matter hypodensities and bilateral calcification of the basal ganglia. The mechanism for the folate deficiency and altered ratio of plasma to cerebrospinal fluid folate is unknown, but the deficiency may be responsive to replacement therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50301/1/410130620_ftp.pd

Autoantibodies to folate receptors in the cerebral folate deficiency syndrome

In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but folate levels in the serum and erythrocytes are normal. We examined serum specimens from 28 children with cerebral folate deficiency, 5 of their mothers, 28 age-matched control subjects, and 41 patients with an unrelated neurologic disorder. Serum from 25 of the 28 patients and 0 of 28 control subjects contained high-affinity blocking autoantibodies against membrane-bound folate receptors that are present on the choroid plexus. Oral folinic acid normalized 5MTHF levels in the cerebrospinal fluid and led to clinical improvement. Cerebral folate deficiency is a disorder in which autoantibodies can prevent the transfer of folate from the plasma to the cerebrospinal fluid. Copyright © 2005 Massachusetts Medical Society