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We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic disease widespread in the world. Sardinia represents, together with Finland, the region with the highest incidence of type 1 DM (DM1), as well as a high prevalence of gestational DM (GDM). Despite the improvement in obstetric surveillance, perinatal and long-term adverse outcomes are still frequent in the offspring of diabetic mothers. During gestations complicated by DM, fetal heart is one of the most affected organ potentially undergoing structural heart defects or several degrees of fetal myocardium hypertrophy and impaired cardiac function. The aim of our study was to evaluate, through echocardiographic examination, cardiac features and performance in a South Sardinian population of newborns of diabetic mothers comparing them to a group of control subjects. In our sample, the E/A ratio resulted a significant marker of early diastolic dysfunction in asymptomatic neonates born by diabetic mothers, even if such result should be confirmed on larger samples. [ABSTRACT FROM AUTHOR]