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

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 < 0.001). The use of normal serum ALT levels to predict DJS among neonates with cholestasis had a sensitivity of 93%, specificity 90%, positive predictive value (PPV) 34%, and negative predictive value (NPV) 99.5%. The median UCPI% was significantly higher in DJS patients [88%, interquartile range (IQR) 1–IQR3, 84.2%–92.7%] than in NC from other causes [67%, (IQR1–IQR3, 61%–71.5%; Confidence interval 0.18–0.28; P < 0.001)]. The use of UCPI% >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%.