Folate responsive neuropathy

The literature on folate related neuropathy has been reviewed. Twenty patients fulfilled the following criteria (a) they presented with neurological findings for which no other cause could be found (b) the serum or red cell and/or the CSF folate was low (c) the serum vitamin B12 or vitamin B12 absorption was normal and (d) they showed a significant response to folic acid. Ten presented with a peripheral neuropathy, eight with subacute combined degeneration of the cord and two with a myelopathy. In two patients the neuropathy occurred when treatment for congenital malabsorption of folate--an isolated lesion affecting folate alone--lapsed. Two patients with subacute combined degeneration died and posterio-lateral sclerosis of the cord was confirmed at autopsy. Three patients were mentally retarded and nine showed mental changes which also responded to folate in addition to the neurological disorder. A single biochemical reaction, the methionine synthetase reaction, is suggested as the basis for the neurological as well as the haematological consequences of both vitamin B12 and folate deficiency. The pitfalls in diagnosis are discussed and a greater awareness of the condition urged.