Cerebral folate deficiency

Cerebral folate deficiency is a syndrome in which the folate form 5-methyltetrahydrofolate is low in the cerebrospinal fluid even though blood levels are normal, so the brain is short of folate while the rest of the body is not. Symptoms typically begin between about 5 and 24 months of age and, untreated, can include poor muscle tone, trouble with coordination and speech, and seizures. One cause is a mutation in FOLR1, a gene for folate transport, inherited in an autosomal recessive pattern; others include Kearns-Sayre syndrome, autoantibodies against the folate receptor, and metabolic errors such as 5,10-methenyltetrahydrofolate synthetase deficiency. Because correcting folate in the body does not correct the brain deficiency, affected people are treated with folinic acid, and success depends on starting early and continuing for long periods. Fewer than 20 people with the FOLR1 defect have been described in the medical literature.