Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Thai infants: Case reports on clinical presentation, genotype analysis, and considerations for negative newborn screening

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a rare autosomal recessive metabolic liver disease caused by mutations in the SLC25A13 gene. This study presents three cases of NICCD in Thai infants, all of them exhibited cholestatic jaundice as their primary clinical presentation, with varying degrees of severity. Their symptoms spontaneously resolving between 5 to 20 months of age. Interestingly, citrulline levels in these infants did not consistently indicate elevated levels as seen in previous studies, highlighting the need for more sensitive newborn screening tests. Additional molecular testing is crucial for accurate diagnosis, with the most common mutation being p.Met285Profs*2. Implementing a second-tier molecular test based on common mutations can enhance diagnostic accuracy. Further research into genotype-phenotype correlations within the Thai population is essential to refine NICCD screening and diagnostic strategies.