P546: Assessment of inborn errors of metabolism genes on the Recommended Uniform Screening Panel using the ClinGen Clinical Validity framework

Methods: Patients less than 18 years old seen by the clinical genetics consult service who underwent clinical rapid genetic testing, including rGS, rapid exome sequencing, and neonatal crisis panel analysis, sent to one of two third-party labs between March 2020 and January 2024 were eligible for this study.Recommendations for clinical testing were at the sole discretion of the attending clinical geneticist.Patients' guardians were approached for the study at the time of clinical consent.Those who consented had a second sample collected for in-house rGS to be performed concurrently with the clinical send-out testing.Patients were primarily recruited from inpatient hospital units, though some were enrolled from ambulatory clinics.Demographic data including age, race, ethnicity and preferred language, and Child Opportunity Index (COI) domains were compared between patients who enrolled and those who did not.When available, reasons for declining participation were recorded without identifying or demographic information.Data from only patients whose samples were sent to one of the third-party labs are presented here, due to data availability, with plans to analyze the full cohort once additional data are available.Results: One-hundred twenty-seven of 175 patients (72.6%) receiving a qualifying clinical genetic test from the third-party lab enrolled in the study.There were no statistically significant differences in the sex of study enrollers (33.1% female) compared to non-enrollers (47.9% female).The enrollers did not significantly differ in racial composition, with 67.7% of enrollees identified as White compared to 54.4% in the non-enrolled group.A significantly higher proportion of English-speaking patients were enrolled in the study (91.3%) compared to non-enrollers (77.1%) (Chi-square, p = 0.022).The non-enrolled group also lived in areas with statistically significantly lower education, health and composite COI.Frequently cited reasons for declining participation across both labs included lack of interest in research (n=23), feeling overwhelmed (n=13), aversion to additional patient blood draws (n=5), aversion to additional parental blood draws (n=2), privacy concerns (n=1), and other (n=8).For two of the non-enrollers, participation in the research was stated not to have been offered.A stated reason for not enrolling was unavailable for 9 patients.Conclusion: Our findings suggest that language is a barrier to research participation.Although no significant differences in race or ethnicity were observed, the difference in preferred language underscores the need for more inclusive recruitment strategies for non-English-speaking patients.Additionally, patients from areas with lower COI were less likely to enroll.Previous research has highlighted that socioeconomic status is associated with barriers to genomic research participation, including lower education attainment, limited genomic knowledge, financial constraints, and reduced understanding of research processes.Ongoing research will expand to analyze the full cohort, allowing for a more comprehensive analysis of these patterns and informing strategies to increase participation from diverse patient populations.