Phenotypic features of children with neurodevelopmental diseases in relation to biogenic amines

Area of Science:

• Neuroscience
• Biochemistry
• Pediatrics

Background:

• Disruptions in monoamine metabolism, involving neurotransmitters like dopamine and serotonin, are linked to various neurological dysfunctions.
• Understanding these metabolic alterations is crucial for diagnosing and managing neurodevelopmental disorders in children.

Purpose of the Study:

• To investigate the correlation between clinical phenotypes of neurodevelopmental disorders in children and the levels of dopamine (HVA) and serotonin (5-HIIA) metabolites in cerebrospinal fluid (CSF).
• To identify specific clinical features associated with impaired monoamine turnover.

Main Methods:

• Analysis of cerebrospinal fluid (CSF) for homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIIA) levels in 55 children diagnosed with neurodevelopmental disorders.
• Correlation of metabolite levels with clinical phenotypes, including disorder progression, movement disorders (extrapyramidal syndrome, dystonia, tremor, rigidity), and developmental delays.
• Univariate and multivariate regression analyses were employed to determine significant associations.

Main Results:

• Nearly half (49.1%) of the children exhibited decreased levels of at least one monoamine metabolite.
• Significantly lower levels of both HVA and 5-HIIA were observed in children with progressive disorders and extrapyramidal syndromes.
• Low HVA levels were associated with hypokinetic and regulatory disorders, while low 5-HIIA levels were linked to progressive course, extrapyramidal syndrome, and dystonia. Multivariate analysis confirmed progressive course and rigidity as significant predictors of low HVA, and progressive course for low 5-HIIA.

Conclusions:

• A progressive and rigid phenotype in children with neurodevelopmental disorders indicates a high risk of monoamine deficiency, underscoring the importance of metabolite analysis.
• Conditions such as psychomotor delay with epilepsy and hypotonia are less frequently associated with low monoamine levels.
• Clinical presentations, regardless of the final diagnosis, can be associated with impaired monoamine turnover, highlighting the clinical relevance of these biochemical markers.