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Determination of 5-methyltetrahydrofolate in cerebrospinal fluid of paediatric patients: reference values for a
Aida Ormazabal1, Angels García-Cazorla, Belén Pérez-Dueñas
1Department of Clinical Chemistry, Hospital Sant Joan de Déu, Passeig Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain.
Insights
Cerebral folate deficiency (CFD) is a neurological disorder characterized by low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5-MTHF) levels. This study establishes reference values for pediatric CSF 5-MTHF and identifies elevated CSF total protein as a potential CFD marker.
Area of Science:
- Neurology
- Biochemistry
- Pediatrics
Background:
- Cerebral folate deficiency (CFD) is a neurological syndrome linked to low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5-MTHF) with normal plasma folate.
- Diagnosis of CFD in pediatric patients requires established reference values for CSF 5-MTHF.
Purpose of the Study:
- To analyze CSF 5-MTHF concentrations in a pediatric control population.
- To establish reference values for pediatric CSF 5-MTHF.
- To investigate CSF 5-MTHF levels in pediatric patients with neurological disorders.
Main Methods:
- Analyzed plasma and CSF samples from 63 pediatric controls and 165 pediatric patients with various neurological disorders.
- Measured CSF 5-methyltetrahydrofolate (5-MTHF) using reverse-phase HPLC with fluorescence detection.
- Stratified reference values based on age due to a negative correlation between 5-MTHF and age in controls.
Main Results:
- A negative correlation was observed between CSF 5-MTHF values and age in controls (r=-0.468; p<0.0001).
- Out of 165 patients, 122 had normal CSF 5-MTHF, while 43 exhibited decreased levels.
- Increased CSF total protein was associated with low CSF 5-MTHF concentrations (chi(2)=7.796; p=0.005).
Conclusions:
- The developed method aids in establishing reference values and diagnosing CFD in pediatric patients.
- Elevated CSF total protein concentrations may serve as a marker for potential CFD.
- This study provides crucial diagnostic insights for pediatric neurological disorders related to folate metabolism.
Background:
Cerebral folate deficiency (CFD) has been described as a neurological syndrome associated with low 5-methyltetrahydrofolate (5-MTHF) values in cerebrospinal fluid (CSF) with normal folate concentrations in plasma. Our aim was to analyse CSF 5-MTHF concentrations in a paediatric control population and in patients with various neurological disorders.
Methods:
We studied plasma and CSF samples from 63 paediatric controls (age range: 2 days to 18 years, average: 3.8 years) and from 165 patients (age range: 1 day to 22 years, average: 5.0 years) with severe epileptic encephalopathies of unknown origin, movement disorders, Rett syndrome and mitochondrial diseases. CSF 5-methyltetrahydrofolate was analysed by reverse phase HPLC with fluorescence detection (excitation: 295 nm and emission: 355 nm).
Result:
A negative correlation between 5-MTHF values and age of controls was observed (r=-0.468; p<0.0001) and reference values were therefore stratified into 3 age groups. Regarding patients, 122 out of 165 showed normal CSF 5-MTHF values while 43 showed decreased values ranging from profound to mild deficiencies. Increased CSF total protein values were associated with the presence of low 5-MTHF concentrations (chi(2)=7.796; p=0.005).
Conclusions:
The application of this method has been useful for the establishment of reference values and for diagnosis of CFD in paediatric patients. Furthermore, increased CSF total protein concentrations should be considered as a marker of a possible CFD.
