Determination of 5-methyltetrahydrofolate in cerebrospinal fluid of paediatric patients: reference values for a paediatric population.
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).


RESULTS
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.
Ormazabal
Aida
A
Department of Clinical Chemistry, Hospital Sant Joan de Déu, Passeig Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain.
García-Cazorla
Angels
A
Pérez-Dueñas
Belén
B
Gonzalez
Veronica
V
Fernández-Alvarez
Emilio
E
Pineda
Mercé
M
Campistol
Jaume
J
Artuch
Rafael
R
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004827:Epilepsy / Q000134:cerebrospinal fluid / Q000175:diagnosis; D005453:Fluorescence; D006801:Humans; D028361:Mitochondrial Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis; D009069:Movement Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis; D012016:Reference Values; D015518:Rett Syndrome / Q000134:cerebrospinal fluid / Q000175:diagnosis; D013763:Tetrahydrofolates / Q000134:cerebrospinal fluid*
D013763:Tetrahydrofolates; C005984:5-methyltetrahydrofolate