Spinal fluid 5-methyltetrahydrofolate levels are normal in Rett syndrome

A recent study reported low CSF levels of a folate metabolite, 5-methyltetrahydrofolate (5MTHF), despite normal serum folate from four girls with Rett syndrome (RTT).¹ Treatment with folinic acid increased CSF 5MTHF levels in these girls and their parents reported modest clinical improvement. The authors suggested a pathogenic relationship between CSF 5MTHF and RTT and, thus, a potential treatment. In order to evaluate these findings, we analyzed CSF 5MTHF levels in 76 girls and women with RTT.

Methods.

The protocol and consent form were approved by the Institutional Review Boards of Baylor College of Medicine, University of Alabama–Birmingham (UAB), and the Children’s Hospital of Eastern Ontario (CHEO). Studies were performed in the Clinical Research Centers of the Texas Children’s Hospital (TCH), UAB, or CHEO from October 2003 to October 2004. A history and structured examination was performed on each girl by experienced examiners (J.L.N., S.M.M., D.G., A.P., P.H.) to confirm the diagnosis using consensus criteria.²

All lumbar punctures were performed by J.L.N., S.M.M., M.I., or P.H. using sterile technique. Conscious sedation was accomplished by IV midazolam (0.05 mg/kg) or propofol (2.0 mg/kg). CSF (3.5 mL) was collected into tubes provided by the analytical laboratory and immediately placed on ice. If any discoloration was noted, the tubes were immediately centrifuged and the supernatant placed in fresh tubes. The CSF was placed at −80 °C within 10 minutes of collection and stored at −80 °C until shipped on dry ice to Baylor University Institute of Metabolic Studies, Dallas, TX. Blood was collected for serum folate determination. CSF levels of 5-MTHF and serum folate were determined by HPLC.³

A natural logarithmic transformation was applied to …