Cerebral folate deficiency: a neurometabolic syndrome?
Sarah Mangold1, Nenad Blau, Thomas Opladen
1Department of Pediatrics, University Hospital RWTH Aachen, Germany. smangold@ukaachen.de
Insights
Cerebral folate deficiency (CFD) is not a distinct syndrome for most patients, often resulting from various underlying conditions. However, CFD may be a treatable factor influencing disease progression, warranting further research.
Area of Science:
- Neurology
- Metabolic Disorders
- Pediatrics
Background:
- Cerebral folate deficiency (CFD) is increasingly recognized in pediatric neurological conditions.
- The question remains whether CFD constitutes a distinct clinical syndrome.
Purpose of the Study:
- To investigate the characteristics and potential syndrome definition of cerebral folate deficiency (CFD) in pediatric patients.
Main Methods:
- Retrospective analysis of pediatric patients with low cerebral spinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF) levels.
- Evaluation of clinical symptoms, disease severity, and genetic analysis for folate receptor 1 gene mutations.
Main Results:
- 103 pediatric patients identified with low (n=58) or very low (n=45) 5MTHF levels.
- Leading symptoms included mental and motor retardation, epilepsy, ataxia, and pyramidal tract signs.
- No correlation found between 5MTHF levels and disease severity, duration, specific symptoms, or antiepileptic drug treatment; folate receptor 1 gene mutations were absent.
Conclusions:
- CFD is typically a consequence of diverse underlying processes rather than a distinct neurometabolic syndrome.
- CFD may represent a treatable factor that modifies disease course and warrants prospective investigation.
Background:
Cerebral folate deficiency (CFD) is increasingly recognized in various neurological conditions, raising the question of whether it might represent a clear-cut clinical syndrome.
Methods:
Retrospective analysis of patients with low cerebral spinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF) values was performed.
Results:
58 pediatric patients with low (-2nd to -3rd standard deviation) and 45 patients with very low 5MTHF values (<3rd standard deviation) were identified, including 22 patients with defined underlying neurological conditions. The leading symptoms were mental retardation (n=84), motor retardation (n=75), epilepsy (n=53), ataxia (n=44) and pyramidal tract signs (n=37). There was no relationship between 5MTHF levels and the severity of clinical disease, the duration of clinical disease, distinct neurological symptoms and antiepileptic drug treatment, respectively. Genetical analysis for mutations in the folate receptor 1 gene proved normal in all 16 children studied.
Conclusions:
For the majority of patients CFD is not a clear-cut neurometabolic syndrome but the common result of different genetic, metabolic or unknown processes. Nevertheless, CFD may represent a treatable disease-modifying factor which should therefore be addressed in prospective studies.
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