Rapid and Dramatic Decreases of Cerebral 5-Methyltetrahydrofolate: A Treatable Form of Progressive Neurodegeneration (S28.007)

Abstract

Objective: We provide evidence demonstrating that CSF 5-MTHF decreases over time and in some cases, very quickly. Hence, progressive neurologic symptoms may indicate the development of Cerebral Folate Deficiency (CFD), even if prior determinations were normal. Background The cerebral folate deficiency (CFD) syndrome describes any neurological condition where low levels of CSF 5-methyltetrahydrofolate (5-MTHF) are found within the CNS and where systemic folate levels are normal. CFD can be primary (inherited defect), or secondary (as in mitochondrial disease or an autoimmune disorder). In practice, once CSF 5-MTHF levels are measured, clinicians generally consider CFD excluded if levels are normal. Design/Methods: Nine children were identified with progressive neurologic symptoms that included epilepsy, movement disorders, and neurobehavioral difficulties. Previously documented CSF 5-MTHF levels were normal in all (>50 nmol/L). Eight of nine were scored as Probable or Highly Probably Mitochondrial Disease using the Nijmegen Diagnostic Criteria (Neurology 2002;59:1402). Results: CSF 5-MTHF levels dropped by 44.2% in an average of 37 months, with a majority dropping into the abnormal range. The most dramatic of these was a 50% reduction in CSF 5-MTHF in 9 months. Data regarding treatment outcomes will be presented. Conclusions: Findings suggest that CSF 5-MTHF levels are not static over time and repeat assessment of CSF 5-MTHF should be considered in patients with progressive neurologic abnormalities. Supported by: Medical Neurogenetics, LLC. Disclosure: Dr. Starnes has received personal compensation for activities with Medical Neurogenetics, LLC as an employee. Dr. Shoffner has received personal compensation for activities with Medical Neurogenetics, LLC. Dr. Shoffner holds stock and/or stock options in Medical Neurogenetics, LLC. Dr. Hyland has received personal compensation for activities with Medical Neurogenetics as co-owner.Dr. Hyland has received compensation for serving as the vice president of Medical Neurogenetics.Dr. Hyland has received research support from National Institute of Health and Neurotransmitter Disease Foundation.