Homovanillic acid in cerebrospinal fluid of 1388 children with neurological disorders

Abstract

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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“…In those studies, between 20-37% of the patients were diagnosed with one of the non-neurotransmitter genetic disorders [26,31]. In our cohort, 8 out of the 150 patients (5.3%) had low HVA and 5 (62.5%) of these patients had an underlying inherited neurotransmitter or non-neurotransmitter disorder with a confirmed underlying genetic diagnosis.…”

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