Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency Differentiated from Biliary Atresia

Area of Science:

• Biochemistry
• Pediatric Gastroenterology
• Neonatal Medicine

Background:

• Differentiating neonatal cholestatic liver diseases is critical for timely intervention.
• Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and biliary atresia (BA) present similar symptoms, posing diagnostic challenges.
• Biochemical markers are needed for accurate differentiation.

Purpose of the Study:

• To establish a method for differentiating NICCD from BA using total hexose levels.
• To evaluate the diagnostic utility of total hexose and citrulline in dry blood spots (DBS).

Main Methods:

• Analyzed blood concentrations of amino acids, carnitine, acylcarnitines, and total hexose in DBS from 11 NICCD patients, 29 BA patients, and 4,898 controls.
• Utilized tandem mass spectrometry (MS/MS) for precise biochemical measurements.
• Assessed diagnostic performance using receiver-operating characteristic (ROC) curves.

Main Results:

• Patients with NICCD showed significantly higher blood concentrations of total hexose (15.3 ± 9.0 mmol/L) and citrulline (Cit) (197.9 ± 93.7 µmol/L) compared to BA patients (7.3 ± 2.7 mmol/L and 17.5 ± 7.4 µmol/L, respectively).
• Diagnostic thresholds of total hexose (> 10 mmol/L) and Cit (> 55 µmol/L) demonstrated high specificity (97.8% and 99.1%) and good sensitivity (66.7% and 90.0%) for NICCD.
• Area under the ROC curves for both markers exceeded 0.85, indicating strong diagnostic accuracy.

Conclusions:

• Elevated total hexose levels in DBS, measured by MS/MS, are a valuable biomarker for diagnosing NICCD.
• Combined analysis of total hexose and citrulline levels effectively differentiates NICCD from BA.
• This biochemical approach offers a reliable, non-invasive method for diagnosing NICCD in neonates.