Cerebrospinal Fluid Concentrations of Pterins and Metabolites of Serotonin and Dopamine in a Pediatric Reference Population

Abstract

ABSTRACT. Accurate diagnosis and management of in-group of conditions and not all are associated with characteristic born errors of monoamine neurotransmitter and tetrahy-findings. Indeed, some affected subjects are symptomless. In drobiopterin metabolism depend on reliable reference addition, there are a variety of conditions that may mimic the ranges of key metabolites. Cerebrospinal fluid (CSF) was clinical and/or biochemical picture but that are not due to a collected in a standardized way from 73 children and young primary defect in biopterin metabolism. adults with neurologic disease, with strict exclusions. InIn clinical practice, differential diagnosis, decisions on maneach specimen, concentrations of homovanillic acid (HVA), agement, and monitoring of therapy for the patients with the 5-hydroxyindoleacetic acid (HIAA), total neopterin, 7,8-inborn errors of BH4 metabolism are dependent on the correct dihydrobiopterin, and tetrahydrobiopterin (BH4) were choice and interpretation of biochemical investigations and remeasured using HPLC. There was a continuous decrement quire that reliable reference ranges are available for key metabin CSF HVA, HIAA, and BH4 during the first few years olites. The present article documents such ranges for the followof life; this was independent of height (or length). Age-ing metabolites in CSF: HVA, HIAA, BH4, BH2 (a metabolite related reference ranges for each metabolite are given. of BH4), and NEO (neopterin plus 7,8-dihydroneopterin, derivExtensive correlations between HVA, HIAA, 7,8-dihydro-atives of the BH4 precursor dihydroneopterin triphosphate). biopterin, and BH4 were further analyzed by multiple Although pediatric reference ranges have been established for regression. Age and CSF BH4 were significant explanatory CSF amine metabolites (3-7) and for total biopterins and neopvariables for CSF HIAA, but CSF I-IVA had only HIAA terins (8-12), these have never been generated using the same as a significant explanatory variable. (Pediatr Res 34: 10-CSF samples; therefore, close study of the relationship between 14,1993) these variables has not been possible. These relationships are carefully examined in the present article. Abbreviations MATERIALS AND METHODS

Cerebrospinal fluid studies in children with cerebral malaria: an excitotoxic mechanism?

“…37 5-Hydroxyindoleacetic acid was measured by HPLC with electrochemical detection. 38 Total neopterin (neopterin plus dihydroneopterin, breakdown products of dihydroneopterin triphosphate), tetrahydrobiopterin, and dihydrobiopterin were measured by HPLC with dual electrochemical and fluorometric detection. 38 Nitrate plus nitrite were measured by spectrophotometry.…”

“…38 Total neopterin (neopterin plus dihydroneopterin, breakdown products of dihydroneopterin triphosphate), tetrahydrobiopterin, and dihydrobiopterin were measured by HPLC with dual electrochemical and fluorometric detection. 38 Nitrate plus nitrite were measured by spectrophotometry. 39 Reference ranges for the metabolite concentrations were constructed from children and young adults living in the United Kingdom with a variety of neurologic or metabolic diseases in whom no disturbance of the biochemical pathways was expected; CSF was sampled after at least a 4-hr fast.…”

Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies

“…BH4 deficiency influences the synthesis of catecholamines, serotonin [24] and nitric oxide [25] in the central nervous system (CNS), and measurement of their metabolites in cerebrospinal fluid (CSF) is important for the diagnosis of different forms (severe v. mild) of BH4 deficiencies. Not only the absolute levels of 5-hydroxyindoleacetic acid and homovanillic acid in CSF, but also differences in the ratios of neurotransmitter levels provide important diagnostic information relating to the severity and outcome of BH4 deficiency [26].…”

Pterin determination in cerebrospinal fluid: state of the art

“…The correct diagnosis of these conditions can be achieved through the analysis of HVA, 5-HIAA, 3-OMD, 5-OHT, neopterin, and B in the CSF (Table 1). However, while the analysis of neurotransmitter metabolites can be easily achieved by liquid chromatography coupled to electrochemical detection (ECD) [7] or to mass spectrometry (MS) [8] most of available analytical methods of pterins in CSF cannot allow direct quantification of BH4 [9]. This review will focus on the methods and advances for monitoring pterins in CSF.…”