Perfil metabolômico de amostras de pacientes diagnosticados com doença de Wilson

• Ano de defesa: 2024
• Autor(a) principal: Lopes, Thais de Assis
• Orientador(a): Oliveira, Regina Vincenzi
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Carlos; Câmpus São Carlos
• Programa de Pós-Graduação: Programa de Pós-Graduação em Química - PPGQ
• Palavras-chave em Português: Doença de Wilson; Doenças raras; Metabolômica; Doença hepática; Espectrometria de massas de alta resolução
• Palavras-chave em Inglês: Wilson's disease; Rare diseases; Metabolomic; Liver disease; High resolution mass spectrometry
• Área do conhecimento CNPq: CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ANALITICA; CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ANALITICA::INSTRUMENTACAO ANALITICA
• Link de acesso: https://hdl.handle.net/20.500.14289/22024

Wilson's Disease (WD) or hepatolenticular degeneration, is a rare genetic disorder caused by the ATP7B gene. WD causes the accumulation of copper (Cu) in various body tissues, including the liver, brain, kidneys, and corneas, due to a disorder in Cu metabolism. If left untreated, it can cause liver disease, central nervous system dysfunction, and fatal damage. Early diagnosis of WD is essential to reduce clinical complications. There are no specific biochemical tests for diagnosing WD, but rather a combination of clinical characteristics, including low levels of ceruloplasmin, increased urinary excretion of Cu, high levels of hepatic Cu, and Cu deposits in the cornea. In this study, we used a global metabolomics approach with liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) to identify changes in metabolic pathways in plasma and urine samples from individuals with WD compared to healthy individuals (control group). The statistical analysis showed that 98 molecular features were significantly different in urine samples (p ≤ 0.05 and VIP ≥ 1) and 243 molecular features in plasma samples (p ≤ 0.05 and VIP ≥ 1). Out of these, 139 metabolites were putatively annotated and evaluated for changes in biochemical pathways, which are related to arginine biosynthesis, linoleic acid metabolism, alanine, aspartate, and glutamate metabolism, and biosynthesis of phenylalanine, tyrosine, and tryptophan. These results provide valuable insights into potential pathogenic mechanisms of WD and contribute to discovering biomarkers for rare and neglected diseases. The findings of this study have the potential to aid in developing more accurate diagnoses and treatments for rare and neglected diseases. They also could pave the way for further research on discovering new diagnosis biomarkers.