458 Multi-omic insights and community perspectives in Huntington’s disease: A Puerto Rican cohort study

Objectives/Goals: To integrate proteomic and metabolomic profiling with genetic literacy and patient experience data to uncover biological mechanisms, community perceptions, and barriers to care in Puerto Ricans affected by Huntington’s disease. Methods/Study Population: We conducted a mixed-methods, multi-omic study combining quantitative proteomic and metabolomic analyses with surveys and interviews exploring genetic literacy and access to care. Participants included patients, first-degree relatives, and controls recruited through PR Huntington Foundation (Fundación Huntington Puerto Rico). Plasma samples were analyzed via mass spectrometry to identify differential protein and metabolite expression associated with CAG repeat length, clinical stage, and symptom burden. Qualitative data captured perceptions of genetics, stigma, and support networks. Results/Anticipated Results: Multi-omic analysis revealed disruptions in energy metabolism, oxidative stress response, and mitochondrial pathways, including altered creatine kinase, apolipoproteins, and kynurenine metabolites. These signatures correlated with CAG repeat length and disease severity. Qualitative findings showed limited genetic literacy, lack of formal counseling, and reliance on community organizations for support. Participants emphasized the need for accessible education and culturally adapted care models. Discussion/Significance of Impact: Integrating omics with community insights highlights both biological and social determinants of disease burden. The findings underscore the significance of equitable precision medicine, culturally grounded education, and community partnerships in enhancing care for underserved Huntington’s disease populations.