653 - Assessment of Genetic Sequencing Results in Neonates with Conjugated Hyperbilirubinemia

Publication Number: 653.3986

Priyanka Patel, Los Angeles General Medical Center, Los Angeles, CA, United States; Shoji Yano, LA General Medical Center, University of Southern California, Los Angeles, CA, United States; Lorayne Barton, Keck School of Medicine of USC/Los Angeles General Hospital, Los Angeles, CA, United States; Smeeta Sardesai, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States; Rowena Cayabyab, Los Angeles General Medical Center, Los Angeles, CA, United States

Background: Conjugated hyperbilirubinemia is a heterogeneous diagnosis with a variety of causes. As most neonates are not ultimately diagnosed with a primary liver disorder, all factors contributing to hepatobiliary dysfunction may remain unclear. Advancements in genetic studies have allowed for the analysis of these factors to better identify and potentially direct treatment in neonates with this diagnosis.

Objective: The objective of this study was to assess how completed genetic testing in neonates contributed to the understanding of the pathophysiology of direct hyperbilirubinemia in patients and determine its effects on clinical management.

Design/Methods: A retrospective chart review was conducted of all patients admitted to Los Angeles General Medical Center's Neonatal Intensive Care Unit between January 2020 and February 2024 with the diagnosis of cholestasis or cholestatic jaundice. Data was collected from the hospital's designated electronic medical record and clinical database. Exclusion criteria included repeat associations with the same patients. Descriptive analysis was completed with the use of Microsoft Excel.

Results: There were 25 encounters with the diagnosis of cholestasis or cholestatic jaundice that were analyzed; of these encounters, 19 patients were included in the study. The included patients had a median gestational age of 27 (25, 31) weeks, median birth weight of 795 (700, 1220) grams, and median direct bilirubin of 5.2 (4.3, 5.6) mg/dL with testing completed at a mean post-menstrual age of 36 (34, 40) weeks. Of these neonates, eight patients completed testing with targeted gene sequencing panels of genes associated with hyperbilirubinemia. One patient completed whole exome sequencing in the setting of multiple congenital anomalies. Five patients were identified to have pathogenic variants in genes associated with hyperbilirubinemia. Whole exome sequencing of the single patient revealed multiple variants of uncertain significance in genes that are not associated with direct hyperbilirubinemia. (Table)

Conclusion(s): Preliminary data demonstrated that some neonates with conjugated hyperbilirubinemia were discovered to have pathogenic variants in genes associated with hyperbilirubinemia. Neonates who completed genetic testing for other diagnoses require additional analysis and assessment of how this testing may have affected clinical management.

Table 1.
Demographic characteristics of neonates who completed genetic testing.