Comprehensive metabolomics analysis reveals novel biomarkers and pathways in falsely suspected glutaric aciduria Type-1 newborns.

BACKGROUND: Glutaric aciduria type-1 (GA-1) is a rare metabolic disorder due to glutaryl coenzyme A dehydrogenase deficiency, causing elevated levels of glutaryl-CoA and its derivatives. GA-1 exhibits symptoms like macrocephaly, developmental delays, and movement disorders. Timely diagnosis through genetic testing and newborn screening is crucial. However, in some cases, transiently elevated level of glutarylcarnitine (C5DC) challenges accurate diagnosis, highlighting the need for alternative diagnostic methods, like mass spectrometry-based untargeted metabolomics, to identify additional biomarkers for distinguishing falsely suspected GA-1 from healthy newborns. METHODOLOGY: DBS samples from falsely suspected GA-1 newborns (n = 47) and matched control were collected through the NBS program. Untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) was performed to enable biomarker and pathway investigations for significantly altered metabolites. RESULTS: 582 and 546 were up- and down-regulated metabolites in transient GA-1. 155 endogenous metabolites displayed significant variations compared to the control group. Furthermore, our data identified novel altered metabolic biomarkers, such as N-palmitoylcysteine, heptacarboxyporphyrin, 3-hydroxylinoleoylcarnitine, and monoacylglyceride (MG) (0:0/20:1/0:0), along with perturbed metabolic pathways like sphingolipid and thiamine metabolism associated with the transient elevated C5DC levels in DBS samples. CONCLUSIONS: A distinct metabolic pattern linked to the transient C5DC elevation in newborns was reported to enhance the prediction of the falsely positive cases, which could help avoiding unnecessary medical treatments and minimizing the financial burdens in the health sector.

Eficacia de la Memantina en pacientes con daño cerebral por adicción a drogas / Efficiency of Memantina in patients with cerebral hurt for addiction of drugs

Objetivo: evaluar la acción medicamentosa con Memantina en pacientes con daño cerebral como consecuencia de su adicción al alcohol, cocaina y/o nicotina. Métodos: Se realizó un estudio de intervención autocontrolado con una muestra de 20 pacientes con daño cerebral por adición al alcohol, cocaína y/o nicotina, los pacientes se valoraron al inicio del estudio y después de un año de tratamiento con Memantina. Los insrumentos utilizados fueron el Cuestionario Sevilla de Calidad de Vida (CSCV) y el SPECT cerebral. Para el análisis de los datos se utilizaron los contrastes estadísticos no paramétricos de Wilcoxon y de homogeneidad marginal para muestras relacionadas. Resultados: Los puntajes obtenidos en la Escala de Sevilla muestran una mejoría significativa (p menor que 0.001) después del tratamiento con MEmantina en las escalas favorable (p menor que 0.001) y desfavorable (p menor que 0.001). La evaluación del SPECT cerebral mostró cambios significativos en la perpfusión cerebral (p menor que 0.001) y una reducción de la atrofia cerebral (p menor que 0.001). Conclusiones: El uso de memantina en Adictos a dosis de 5mg, al día durante 1 año, restaura la perfusión sanguínea y mejora los signos indirectos de Atrofia cerebral evidenciado por el Spect Cerebral.

Purpose: To evaluate the action medicated with Memantine in patients with brain damage as a result of his addiction to alcohol, cocaine and/or nicotine. Method: an intervention study autocontrolado with a sample of 20 patients with brain damage by addiction to alcohol, cocaine and/or nicotine, patients were assessed at baseline and after one year of treatment with Memantine. The instruments used were the Questionnaire Seville Quality of Life (CSCV) and Brain SPECT. For data analysis contrasts were used nonparametric Wilcoxon statistical and sample homogeneity marginally related. Results: The scores obtained in the scale of Seville showed a significant improvement (p menor que 0.001) after treatment with Memantine on the scales favourable (p menor que 0.001) and negative (p menor que 0.001). The evaluation of brain SPECT showed significant changes in cerebral perfusion (p menor que 0.001) and a reduction in brain atrophy (p menor que 0.001). Conclusions: The use of memantine in addicts at doses of 5mg. The day for 1 year, restores blood perfusion evidenced by the Brain Spect. The use of this product improves indirect signs of brain atrophy as evidenced by the Brain Spect.