Total folate and 5-methyltetrahydrofolate in the cerebrospinal fluid of children: correlation and reference values.
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.
Tomoyuki
T
Akiyama
Hiroko
H
Tada
Tsugumi
T
Shiokawa
Katsuhiro
K
Kobayashi
Harumi
H
Yoshinaga
D000293:Adolescent; D002526:Cerebellar Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D042241:Early Diagnosis; D005492:Folic Acid / Q000134:cerebrospinal fluid*; D005494:Folic Acid Deficiency / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D006801:Humans; D007223:Infant; D012016:Reference Values; D053719:Tandem Mass Spectrometry; D013763:Tetrahydrofolates / Q000134:cerebrospinal fluid*
D013763:Tetrahydrofolates; D005492:Folic Acid; C005984:5-methyltetrahydrofolate