Cerebral folate deficiency

Fig. 6.3.2a-c Chromatogram of 5MTHF using electrochemical detection, a Standard, 100 nM b control cerebrospinal fluid (CSF) c CSF from a patient with cerebral folate deficiency (CFD)... 

Ramaekers VT, Blau N (2004) Cerebral folate deficiency. Dev Med Child Neurol 46 843-851... 

Ramaekers VT, Rothenberg SP, Sequeira J, Opladen T, Blau N, Quadras EV, Selhub J (2005) Autoantibodies to folate receptors in the cerebral folate deficiency syndrome.. Ns Engl J Med 352 1985-1991... 

Cerebral folate deficiency is caused by antibodies that inhibit active folate transport to the brain. It can be treated with folinic acid. 

Gordon, N., 2009. Cerebral folate deficiency. Developmental Medicine Child Neurology. 51 180-182. 

Inborn errors of folate metabolism also shed light on the role of folates and products of folate metabolism in neurological function. Disorders that result in decreased levels of 5-CH3-THF in the central nervous system are frequently associated with development of seizures e.g. MTHFR deficiency, DHFR deficiency, MTHFDl deficiency, and autoimmune or genetic cases of cerebral folate deficiency due to malfunction of folate receptor alpha). Adult onset cases of MTHFR deficiency have in some cases been associated with psychosis. 

Varadi and Elwis (V3) found low erythrocyte folates in 10 of 81 hospital patients over the age of 70 years. They were suffering from a variety of disorders which included senile dementia, cerebral thrombosis, and arthritis. None had a megaloblastic anemia. Thirty nine percent of ed people admitted to the hospital in the London area were found to have a low serum folate (H29). Read (R15) in another study found that 40 (78%) of 51 people admitted to an old peoples home were folate deficient with a serum concentration below 6 p,g/liter and in three the concentration was below 3 Xg/liter. In an apparently healthy control group of similar age all had levels... 

Steinfeld, R., Grapp, M., Kraetzner, R., Dreha-Kulaczewski, S., Helms, G., Dechert, P., Wevers, R., Grosso, S., and Gartner J., 2009. FDolate receptor alpha defect causes cerebral folate transport deficiency a treatable neuro-degenerative disorder associated with disturbed myelin metabolism. American Journal of Human Genetics. 85 354-363. 

In view of the discrepancies between studies, it is important to note that a low serum B12 level is not necessarily a cause of neurologic damage. Less than 10% of patients with pernicious anemia have clinical neurologic complications, perhaps because stores in different organs are variably depleted (Reynolds, 1976). Cerebral disease may be related to coexistent deficiencies of other vitamins, such as folate, or to the duration of Bi2 deficiency (Reynolds, 1976). In general, the prognosis for cognitive recovery is related to the duration of illness and not to absolute vitamin levels. No criteria have been established to indicate clearly which patients will improve. 

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