neonatal intrahepatic cholestasis due to citrin deficiency

Neonatal intrahepatic cholestasis due to citrin deficiency is a condition that affects the liver of newborns, leading to symptoms such as low birth weight, failure to thrive, and transient cholestasis. It is caused by genetic alterations in the SLC25A13 gene, which plays a key role in liver metabolism. This autosomal recessive condition is identified in the neonatal period, and its exact prevalence is not well established. The clinical picture is generally mild, but a variety of liver dysfunctions may be observed.

The clinical features of this condition predominantly relate to liver dysfunction. Affected newborns may present with low birth weight and failure to thrive along with signs of transient intrahepatic cholestasis. Laboratory studies consistently reveal a range of liver-related abnormalities such as macrovesicular and microvesicular hepatic steatosis, conjugated hyperbilirubinemia, elevated plasma citrulline, increased serum bile acid concentration, and elevations in liver enzymes including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase. Additionally, other biochemical disturbances such as hyperargininemia, hypermethioninemia, hyperthreoninemia, hyperlysinemia, and hypertyrosinemia are always present, reflecting a cluster of metabolic alterations. Not all individuals experience every feature, and severity varies considerably.

The condition is caused by pathogenic variants in the SLC25A13 gene, which is essential for normal liver function and metabolism. In neonatal intrahepatic cholestasis due to citrin deficiency, these genetic alterations disrupt metabolic pathways, leading to the array of hepatic and biochemical abnormalities observed. It is inherited in an autosomal recessive manner, meaning that an affected child inherits one mutated copy of the gene from each parent. Families are encouraged to seek genetic counseling, as this provides important guidance on recurrence risks and family planning.

Currently, management focuses on supportive care and symptom management, tailored to the individual needs of the patient. Because there are no approved or foundational therapies specifically for this condition, treatment involves a multidisciplinary approach that emphasizes regular surveillance to monitor liver function and metabolic status. This supportive care strategy may include nutritional support and interventions focused on addressing hypoglycemia and other metabolic disturbances. Patients and families are advised to discuss available options with their healthcare team and consider genetic counseling to better understand the condition and its implications.

Outcomes in neonatal intrahepatic cholestasis due to citrin deficiency vary depending on the severity of the metabolic disturbances and the timeliness of supportive interventions. With current standards of care, many individuals achieve stabilization of liver function and improved overall health during infancy and beyond. Outcomes described in medical literature continue to evolve as standards of care improve, and regular monitoring helps to identify and manage complications early. Families may find it helpful to connect with specialists experienced in metabolic and liver disorders, and genetic counseling can provide additional guidance for long-term management and family planning.