Urinary coproporphyrins as a diagnostic biomarker of Dubin-Johnson syndrome in neonates: A diagnostic pathway is proposed

Abstract

Background: Dubin-Johnson syndrome (DJS) presents during the neonatal period with a phenotype that overlaps with a broad list of causes of neonatal cholestasis (NC), which makes the identification of DJS challenging for clinicians. We conducted a case-controlled study to investigate the utility of urinary coproporphyrins (UCP) I% as a potential diagnostic biomarker. Methods: We reviewed our database of 533 cases of NC and identified 28 neonates with disease-causing variants in ATP-binding cassette-subfamily C member 2 (ABCC2) gene “Cases” (Study period 2008–2019). Another 20 neonates with cholestasis due to non-DJS diagnoses were included as “controls.” Both groups underwent UCP analysis to measure CP isomer I percentage (%). Results: Serum alanine aminotransferase (ALT) levels were within the normal range in 26 patients (92%) and mildly elevated in 2 patients. ALT levels were significantly lower in neonates with DJS than in NC from other causes (P 80% to predict DJS had a sensitivity, specificity, PPV, and NPV of 100%. Conclusion: Based on the results from our study, we propose sequencing of the ABCC2 gene in neonates with normal ALT, presence of cholestasis and UCP1% >80%.

Keywords

• abcc2gene
• dubin-johnson syndrome
• neonatal cholestasis
• saudi arabia
• urinary coproporphyrins