ASSOCIATION OF CEREBROSPINAL-FLUID DEFICIENCY OF 5-METHYLTETRAHYDROFOLATE, BUT NOT S-ADENOSYLMETHIONINE, WITH REDUCED CONCENTRATIONS OF THEACID METABOLITES OF 5-HYDROXYTRYPTAMINE AND DOPAMINE

1. Folate deficiency, or inborn errors of folate metabolism, cause red uced turnover of 5-hydroxytryptamine (serotonin), and perhaps dopamine , in the central nervous system. The mechanism by which this occurs ar e not known. One possibility is that this is mediated by deficiency of the methyl-donor S-adenosylmethionine. 2. To test this in humans, we have measured cerebrospinal fluid concentrations of 5-hydroxyindoleace tic acid and homovanillic acid, metabolites of 5-hydroxytryptamine and dopamine, respectively, in children with inborn errors of the methyl- transfer pathway. These children are naturally deficient in 5-methylte trahydrofolate, S-adenosylmethionine or both before treatment, and rep lete with S-adenosylmethionine, but not necessarily with 5-methyltetra hydrofolate, during treatment. 3. Children with subnormal cerebrospina l fluid concentrations of 5-methyltetrahydrofolate had significantly r educed concentrations of 5-hydroxyindoleacetic acid and homovanillic a cid. Children with subnormal cerebrospinal fluid concentrations of S-a denosylmethionine did not have significantly reduced concentrations of these metabolites. 4. We conclude that the mechanism by which deficie ncy of 5-methyltetrahydrofolate causes reduced 5-hydroxytryptamine and dopamine turnover is unlikely to be mediated by S-adenosylmethionine.