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Unique metabolic profiles identified in Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) patients

Study finds several metabolites correlated with severity of PANS

Study finds several metabolites correlated with severity of PANS

Metabolomics is the study of small molecules in cells, body fluids, and tissues that reflect underlying biochemical activity. Metabolite analysis has been useful in identifying potential biomarkers for various neuroimmune-psychiatric diseases. Currently, there are no systematic metabolomics datasets for PANS patients.

In this observational study, Murgia et al. performed metabolite analysis on 34 patients with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and 25 healthy subjects to determine whether specific serum metabolic patterns could be identified, as measured through 1H-NMR spectroscopy. 1

This study identified “a set of hydrophilic metabolites that appears to represent a specific pattern characterizing the PANS condition.”

The authors found abnormal levels of serum metabolites in PANS patients, significantly different from that of healthy children, which were associated with neurotransmission (tryptophan, glycine, histamine/histidine) and generalized energy deficiency, oxidative stress neuroinflammation (glutamine, 2-Hydroxybutyrate and, potentially, the tryptophan-kynurenine pathway).

Study Findings:
  • In PANS patients, 2-Hydroxybutyrate and glycerol were found to be increased, while asparagine, glycine, glutamine, histidine, tryptophan and tyrosine were found to be decreased. Whereas, glycine, tryptophan and tyrosine were found to be significantly correlated with severity of PANS symptoms.
  • The amino acid tryptophan (Trp) was found at lower serum concentrations in patients with PANS than in controls, and this metabolite negatively correlated with the severity of PANS.

    Interestingly, a decrease in Trp level has been previously reported in major depressive disorder, schizophrenia, and exhaustion disorder. One Trp metabolic pathway has been recognized as crucial to immunoregulatory mechanisms, neuroinflammation, and microglial activation.

  • Glycine was also shown to be significantly decreased in the serum of PANS patients compared to healthy controls, and was directly correlated with severity of PANS.

    Glycine is widely distributed in the CNS, and is the main neurotransmitter in inhibitory interneurons of the spinal cord, brainstem, and other brain regions involved in processing sensorimotor information and locomotor behavior. It has also been previously reported that glycine acts as a co-agonist of the NMDA receptor.

  • The specific plasma metabolites observed in the present study might reflect specific changes in metabolic pathways induced by inflammation, blood-brain barrier breakdown, and dysregulation of energy metabolism.

Case report: SARS-CoV-2 related paediatric acute-onset neuropsychiatric syndrome (PANS)

SARS-CoV-2 related paediatric acute-onset neuropsychiatric syndrome (PANS)

In this case report, the authors describe two pediatric patients who developed an abrupt onset of psychiatric symptoms following an infection with the SARS-CoV-2 virus. 2

The patients, ages 12 and 13, experienced a sudden onset of psychiatric symptoms including OCD-like behaviors, restricted food intake or eating abnormalities, aggressiveness, hyperactivity, irritability, severe emotional lability, and motor and vocal tics. Testing for ASO, DNAse B, as well as other infections was negative. Both patients tested positive for COVID-19.

Two weeks after a diagnosis of COVID-19, two adolescents developed new-onset OCD, neuropsychiatric, and motor dysfunction symptoms consistent with PANS.

“Our two cases show a temporal correlation between COVID-19 and the onset of PANS. Therefore, it is possible that, in these cases, the SARS-CoV-2 virus has caused PANS, although this cannot be confirmed.”

“SARS-CoV-2 needs to be acknowledged in the differential diagnosis of PANS.” 2

  1. Murgia F. et al. Metabolomic Characterization of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Frontiers in Neuroscience, May 28, 2021.
  2. SARS-CoV-2 related paediatric acute-onset neuropsychiatric syndrome. Pavone, Piero et al. The Lancet Child & Adolescent Health, Volume 5, Issue 6, e19 - e21.

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Digital Information Packet

To learn more about infection-triggered basal ganglia encephalitis syndromes, such as PANS/PANDAS, view our online informational packet. We have compiled journal articles and video clips that may be helpful to you.