Neuropediatrics. 2005 Dec;36(6):380-5.
Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid
Ormazabal A, Artuch R, Vilaseca MA, Aracil A, Pineda M.
Abstract
BACKGROUND: Previous studies in Rett syndrome (RS) patients suggested various abnormalities in biogenic amines, pterins, and folate values in cerebrospinal fluid (CSF). Our aim was to analyse these metabolites in CSF of 16 RS patients (age range: 2 - 23 years). Biogenic amines, pterins, and 5-methyltetrahydrofolate were measured by HPLC with electrochemical and fluorescence detection. RESULTS: CSF values of 5-methyltetrahydrofolate were decreased in 8 out of 16 RS patients (average: 53.6 nmol/L; range: 19 - 92) when compared with our reference values (average: 74.6 nmol/L; range: 45 - 127). These eight patients had epilepsy, while 4 out of 16 RS patients who did not have epilepsy showed normal CSF 5-methyltetrahydrofolate concentrations. Values of biogenic amines or pterins were decreased in four of the patients with low values of 5-methyltetrahydrofolate. No correlation was observed between CSF values of 5-methyltetrahydrofolate and pterins, biogenic amines, or age. Supplementation with folinic acid was applied in six out of the eight patients with CSF 5-methyltetrahydrofolate deficiency. An improvement was noticed in all cases. CONCLUSIONS: An important percentage of RS patients showed 5-methyltetrahydrofolate concentrations under the reference values. Therefore, analysis of CSF 5-methyltetrahydrofolate seems advisable in RS, especially in patients with epilepsy and those resistant to antiepileptic drugs.
Lay Summary
The cerebrospinal fluid (CSF) can be considered a window into the brain. The CSF is basically a saline solution that acts as a buffer for the brain; it is a clear bodily fluid that occupies the space between the skull and brain. Thus, researchers may examine the levels of various biological compounds in the CSF, as a diagnostic tool for a variety of neurological disorders. In this report, the CSF in 16 Rett patients were analyzed. Interestingly, a group of patients displayed a lower range of one compound (5-methyltetrahydrofolate), especially in those who also displayed epilepsy. A precursor of 5-methyltetrahydrofolate, folinic acid, was supplemented in a group of these girls. Interestingly, improved clinical responses were observed after folinic acid treatment. In summary, although this finding in not new (a more detailed study was similarly reported several years ago) it does stress the importance of CSF analysis of 5-methyltetrahydrofolate in Rett syndrome. Indeed, this finding is interesting knowing the role of folate in the regulation of serotonin and dopamine metabolism, and with regards to the similar misregulation recently implicated in the breathing disturbances witnessed in MeCP2-deficient mice.