Perinatal Asphyxia May Cause Reduction in CSF Dopamine Metabolite Concentrations

Serrano, Mercedes; Ormazábal, Aída; Pérez‐Dueñas, Belén; Artuch, Rafael; Coroleu, Wifredo; Krauel, Xavier; Campistol, Jaume; García‐Cazorla, Àngels

doi:10.1212/01.wnl.0000265855.13026.dd

Cited by 6 publications

(6 citation statements)

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“…Diseases associated with high HVA values include Angelman syndrome, preterm infants with varying degrees of intraventricular haemorrhage, and one report of carbamyl phosphate synthetase deficiency (urea cycle disorder). Regarding clinical groups of diseases, hypoxic–ischemic and haemorrhagic injuries showed the highest risk of association with impaired HVA values, supporting the previous observations that this group of patients may present a special risk of impaired dopaminergic status …”

Section: Discussionsupporting

confidence: 87%

“…As shown in Table SI, approximately 43% of patients also presented with impaired 5‐HIAA values, indicating that there is probably an alteration in both of the pathways in several conditions and that the underlying mechanisms in those diseases may be non‐specific. Disturbances in 5‐HIAA have been reported to be even more frequent than HVA defects, suggesting that serotonin is easily impaired in a broad spectrum of diseases, perhaps owing to its widespread connectivity in different areas of the brain.…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports have reinforced the presence of secondary alterations in biogenic amines in the CSF of neurological patients, most of whom suffer from severe chronic diseases that are intractable from an aetiological point of view . A therapeutic assay with l ‐DOPA/carbidopa could be justified in patients with very low CSF HVA values and clinical features compatible with dopaminergic deficiencies, which might offer new therapeutic options.…”

Section: Discussionmentioning

confidence: 99%

“…There is scientific evidence suggesting that impaired HVA values could be a biomarker for dopamine dysfunction in several neurological diseases in children . In this study, we explored the prevalence of dopaminergic abnormalities in a large cohort of children with neurological disorders and correlated their HVA levels with clinical, radiological, and electrophysiological features.…”

mentioning

confidence: 99%

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Homovanillic acid in cerebrospinal fluid of 1388 children with neurological disorders

Molero-Luís

Serrano

Ormazábal

et al. 2013

Develop Med Child Neuro

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METHOD We studied biogenic amines in 1388 cerebrospinal fluid (CSF) samples from children with neurological disorders (mean age 3y 10mo, SD 4y 5mo; 712 males, 676 females. Correlations among CSF homovanillic acid (HVA) values and other biochemical, clinical, neuroradiological, and electrophysiological parameters were analysed.RESULTS Twenty-one patients with primary dopaminergic deficiencies were identified. Of the whole sample, 20% showed altered HVA. We report neurological diseases with abnormal CSF HVA values such as pontocerebellar hypoplasia, perinatal asphyxia, central nervous system infections, mitochondrial disorders, and other genetic diseases. Overlapping HVA levels between primary and secondary dopamine deficiencies were observed. Prevalence of low CSF HVA levels was significantly higher in neonatal patients (v 2 =84.8, p<0.001). Abnormalities in white matter were associated with low CSF HVA (odds ratio 2.3, 95% confidence interval 1.5-3.5).INTERPRETATION HVA abnormalities are observed in various neurological diseases, but some are probably an unspecific finding. No clear limits for CSF HVA values pointing towards primary diseases can be stated. We report several neurological diseases showing HVA alterations. No neuroimaging traits were associated with low HVA values, except for white matter abnormalities. Dopamine and serotonin are neurotransmitters involved in several neurological and systemic functions. Their turnover in the central nervous system (CNS) can be assessed by biochemical analysis of several biogenic amines in cerebrospinal fluid (CSF) at are closely related to them.1-4 Homovanillic acid (HVA), which is the final product in dopamine catabolism, can be used as a marker of dopamine metabolism. Dopamine is synthesized from tyrosine by tyrosine hydroxylase (EC1.14.16.2), which converts tyrosine into L-3,4-dihydroxyphenylalanine (L-DOPA) with tetrahydrobiopterin as a cofactor. Aromatic L-amino-acid decarboxylase (EC4.1.1.28) transforms L-DOPA into dopamine using pyridoxal-5′-phosphate as a cofactor. Dopamine is catabolysed by monoamino oxidase (MAO, EC1.4.3.4) and catechol-O-methyltransferase (EC2.1.1.6), yielding HVA as the stable final product (Fig. S1, online supporting information). Acquired and genetic neurological diseases associated with dopaminergic dysfunction are known to cause movement disorders and neuropsychiatric disorders. There is scientific evidence suggesting that impaired HVA values could be a biomarker for dopamine dysfunction in several neurological diseases in children. 1,2,[5][6][7][8][9] In this study, we explored the prevalence of dopaminergic abnormalities in a large cohort of children with neurological disorders and correlated their HVA levels with clinical, radiological, and electrophysiological features. laboratory. The samples were collected from patients with several neurological disorders for which a diagnostic lumbar puncture was indicated. The samples originated from several hospitals in Spain, Portugal, Greece, Turkey, Argentina, and India. Three hundred...

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Homovanillic acid in cerebrospinal fluid of 1388 children with neurological disorders

Molero-Luís

Serrano

Ormazábal

et al. 2013

Develop Med Child Neuro

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“…However, this preliminary data allowed us to select 'high risk' populations in which, we believe, neurotransmitter studies are especially worthwhile. Our present experience with a reasonable number of CSF samples in different neurological disturbances and ages has given us the chance to describe patterns of disturbances in neurotransmitters in perinatal asphyxia, 24 Lesch-Nyhan disease, pontocerebellar hypoplasia, and different kinds of leukodystrophy. Studying these selected populations we aim not only to describe biochemical changes, but also to hypothesize on new therapeutical approaches.…”

Section: (3) Neurogenetic Conditionsmentioning

confidence: 94%

Secondary abnormalities of neurotransmitters in infants with neurological disorders

García‐Cazorla

Serrano

Pérez‐Dueñas

et al. 2007

Develop Med Child Neuro

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Neurotransmitters are essential in young children for differentiation and neuronal growth of the developing nervous system. We aimed to identify possible factors related to secondary neurotransmitter abnormalities in pediatric patients with neurological disorders. We analyzed cerebrospinal fluid (CSF) and biogenic amine metabolites in 56 infants (33 males, 23 females; mean age 5.8mo [SD 4.1mo] range 1d-1y) with neurological disorders whose aetiology was initially unknown. Patients were classified into three clinical phenotypes: epileptic encephalopathy, severe motor impairment, and non-specific manifestations. All patients showed normal results for screening of inborn errors of metabolism. We report clinical, neuroimaging, and follow-up data. Among the patients studied, 10 had low homovanillic acid (HVA) levels and in four patients, 5-hydroxyindoleacetic acid (5-HIAA) was also reduced. Patients with neonatal onset had significantly lower levels of HVA than a comparison group. HVA deficiency was also associated with severe motor impairment and the final diagnosis related to neurodegenerative disorders. 5-HIAA values tended to be decreased in patients with brain cortical atrophy. The possibility of treating patients with L-Dopa and 5-hydroxytryptophan, in order to improve their neurological function and maturation, may be considered.Brain neurotransmission is essential in young children, not only for interneuronal communication but also for differentiation, neuronal growth, and shaping and wiring of the nervous system. 1 Biogenic amines are the most representative group among brain neurotransmitters 2 and are composed of catecholamines (dopamine and norepinephrine) and serotonin. Within the central nervous system, the final metabolite for dopamine is homovanillic acid (HVA) and for serotonin, 5-hydroxyindoleacetic acid (HIAA). These metabolites can be measured in the cerebrospinal fluid (CSF). Low concentrations of biogenic amine metabolites in the CSF are mainly due to defects in their biosynthetic and catabolic pathways. Deficiencies of tyrosine hydroxylase, aromatic L-amino acid decarboxylase, guanosine triphosphate cyclohydrolase (GTPCH), and sepiapterin reductase, 3 (the last two enzymes contributing to the formation of tetrahydrobiopterin [BH4]), cause the main paediatric neurotransmitter diseases.Little is known about secondary causes of low CSF biogenic amine metabolites, and, to our knowledge, no study focusing on how diverse neurological disorders in infants could affect brain biogenic amines production has been described until now. There are a few studies that have looked at secondary reduction of HVA. It has been reported that epilepsy, 4,5 rapidonset dystonia-parkinsonism, 6 Huntington's disease, 7 and depression and dementia 8,9,10 are among those disorders characterized by secondary reduction of HVA. However, the results found in these studies are often contradictory and not specific to young children. Moreover, no study concerning possible factors that could be related to these secondary abnormalit...

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Biomarkers for the study of catecholamine and serotonin genetic diseases

Ormazábal

Molero-Luís

García‐Cazorla

et al. 2017

Biomarkers in Inborn Errors of Metabolism

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Perinatal Asphyxia May Cause Reduction in CSF Dopamine Metabolite Concentrations

Cited by 6 publications

References 7 publications

Homovanillic acid in cerebrospinal fluid of 1388 children with neurological disorders

Homovanillic acid in cerebrospinal fluid of 1388 children with neurological disorders

Secondary abnormalities of neurotransmitters in infants with neurological disorders

Biomarkers for the study of catecholamine and serotonin genetic diseases

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