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Total folate and 5-methyltetrahydrofolate in the cerebrospinal fluid of children: correlation and reference values
Insights
Cerebral folate deficiency (CFD) can be screened using a total folate (TF) assay in cerebrospinal fluid (CSF). This automated CSF TF test correlates well with 5-methyltetrahydrofolate (5MTHF) levels, aiding early CFD diagnosis.
Area of Science:
- Neurology
- Clinical Biochemistry
- Pediatrics
Background:
- Cerebral folate deficiency (CFD) presents with non-specific neurological symptoms and is often underdiagnosed.
- Accurate CFD diagnosis requires cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF) measurement, a test available only in specialized labs.
- Routine clinical labs commonly perform automated total folate (TF) assays on serum or plasma.
Purpose of the Study:
- To evaluate the utility of an automated CSF total folate (TF) assay as a screening tool for cerebral folate deficiency (CFD).
- To determine if CSF TF levels can reliably estimate CSF 5-methyltetrahydrofolate (5MTHF) concentrations.
Main Methods:
- CSF samples from 73 pediatric patients were analyzed.
- CSF TF, serum TF, and CSF 5MTHF levels were measured.
- CSF 5MTHF was quantified using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) system.
Main Results:
- A strong positive correlation was observed between CSF TF and CSF 5MTHF (ρ=0.930, p<0.0001).
- CSF TF, serum TF, and CSF 5MTHF levels showed negative correlations with patient age.
- The CSF/serum TF ratio did not correlate with age.
Conclusions:
- Automated CSF TF assay is a valuable tool for estimating CSF 5MTHF levels.
- The CSF TF assay can significantly impact the early diagnosis of CFD due to its accessibility compared to the 5MTHF assay.
Background:
Cerebral folate deficiency (CFD) may be underdiagnosed, as it manifests with various non-specific neurological symptoms. The diagnosis of CFD requires a determination of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF), which is available in a limited number of specialized laboratories. In clinical biochemistry laboratories, total folate (TF) determination in serum or plasma is routinely performed by automated analyzers. The aim of this study is to determine whether the automated assay of CSF TF is a helpful screening tool for CFD.
Methods:
We analyzed CSF samples collected from 73 pediatric patients. We measured CSF TF, serum TF, and CSF 5MTHF in 73, 70, and 48 patients, respectively. The assay of 5MTHF was conducted by a newly developed system utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS). We investigated the correlation between TF and 5MTHF in the CSF.
Results:
There was a strong positive correlation between CSF TF and 5MTHF (ρ=0.930, p<0.0001, n=48). Age was negatively correlated with CSF TF (ρ=-0.557, p<0.0001, n=51), serum TF (ρ=-0.457, p=0.0008, n=51), and CSF 5MTHF (ρ=-0.387, p=0.0263, n=33), but not with the CSF/serum TF ratio.
Conclusions:
The automated assay of CSF TF is helpful to estimate CSF 5MTHF. The CSF TF assay may have a significant impact on the early diagnosis of CFD, because clinicians have better access to it than the 5MTHF assay.
