Update on the diagnosis and management of neonatal intrahepatic cholestasis caused by citrin deficiency: Expert review on behalf of the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition

Citrin deficiency is an autosomal recessive metabolic liver disease caused by mutations in the SLC25A13 gene. The disease typically presents with cholestasis, elevated liver enzymes, hyperammonemia, hypercitrullinemia, and fatty liver in young infants, resulting in a phenotype known as "neonatal intrahepatic cholestasis caused by citrin deficiency" (NICCD). The diagnosis relies on clinical manifestation, biochemical evidence of hypercitrullinemia, and identifying mutations in the SLC25A13 gene. Several common mutations have been found in patients of East Asian background. The mainstay treatment is nutritional therapy in early infancy utilizing a lactose-free and medium-chain triglyceride formula. This approach leads to the majority of patients recovering liver function by 1 year of age. Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. Recently, advancements in newborn screening methods have improved the age of diagnosis. Early diagnosis and timely management improve patient outcomes. Further studies are needed to elucidate the long-term follow-up of NICCD patients into adolescence and adulthood. Citrin deficiency: a metabolic disorder causing neonatal cholestasis and steatosis.What is Known image Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder caused by SLC25A13 gene mutations that may recover or progress to liver cirrhosis. SLC25A13 gene mutations may have a late-onset phenotype causing neuropsychiatric symptoms in adulthood.What is New Citrin deficiency has been described in several countries beyond Asia and should be considered in the differential diagnosis of all infants with cholestasis and growth failure. A genetic diagnosis, which is now widely available, is the most reliable tool to confirm citrin deficiency, given the significant variability in both clinical manifestations and genetic mutations. Early diagnosis and treatment results in improved growth and better patient outcomes.