Document Detail

Technical and biochemical factors affecting cerebrospinal fluid 5-MTHF, biopterin and neopterin concentrations.
MedLine Citation:
PMID:  18722797     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The diagnosis of pediatric neurologic disorders with a deficiency in the biosynthesis of either the neurotransmitters serotonin and dopamine, or the co-factor tetrahydrobiopterin or a cerebral 5-methyltetrahydrofolate (5-MTHF) deficiency, strongly relies on a robust analysis of neurotransmitter metabolites, pterins and 5-MTHF in the cerebrospinal fluid (CSF). The aim of this study was to investigate which technical and biochemical factors affect the CSF concentration of 5-MTHF, neopterin and biopterin in a pediatric population. METHODS: We studied effects of the ventriculo-spinal gradient, total protein concentration, pretreatment with ascorbic acid (in case of 5-MTHF analysis), pretreatment of CSF with trichloro acetic acid (TCA)/dithiotreitol (DTE) and oxidation with either iodine or manganese oxide (in case of pterin analysis), storage time and age of the patients. We included CSF samples from children until the age of 18 years and analysed 5-MTHF, neopterin, biopterin, homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and total protein. RESULTS: The major findings of our study are: (1) CSF 5-MTHF, neopterin and biopterin concentrations are not affected by the ventriculo-spinal gradient; (2) pretreatment of CSF with ascorbic acid has negligible effects on 5-MTHF concentrations; (3) pretreatment of CSF with TCA/DTE and oxidation with iodine results in the most accurate determination of neopterin and biopterin; (4) when adjusted for age and total protein, CSF 5-MTHF correlated with 5-HIAA, but not with HVA; (5) the reference value of 5-MTHF in CSF in childhood is age-dependent (r=-0.634; p0.001); (6) we did not observe an age-dependency for neopterin and biopterin in CSF. CONCLUSION: 5-MTHF, neopterin and biopterin can be analysed in any volume of CSF that is collected. For correct analysis of pterins, CSF will have to be pretreated to stabilize the concentrations and stored properly, whereas such pretreatment is not necessary for 5-MTHF.
M M Verbeek; A M Blom; R A Wevers; A J Lagerwerf; J van de Geer; M A A P Willemsen
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-22
Journal Detail:
Title:  Molecular genetics and metabolism     Volume:  95     ISSN:  1096-7206     ISO Abbreviation:  Mol. Genet. Metab.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-22     Completed Date:  2008-12-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805456     Medline TA:  Mol Genet Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  127-32     Citation Subset:  IM    
Department of Laboratory of Pediatrics, Radboud University Nijmegen Medical Centre, Donders Centre for Neuroscience, The Netherlands.
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MeSH Terms
Biopterin / cerebrospinal fluid*,  chemistry
Child, Preschool
Neopterin / cerebrospinal fluid*,  chemistry
Nervous System Diseases / cerebrospinal fluid,  diagnosis*
Specimen Handling
Tetrahydrofolates / cerebrospinal fluid*,  chemistry
Reg. No./Substance:
0/Tetrahydrofolates; 134-35-0/5-methyltetrahydrofolate; 22150-76-1/Biopterin; 670-65-5/Neopterin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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