Hereditary North American Indian childhood cirrhosis

Hereditary North American Indian childhood cirrhosis (NAIC), also known as North American Indian childhood cirrhosis or Cree-Ojibway cirrhosis, is an extremely rare autosomal recessive liver disease that has been identified almost exclusively among children of the Ojibway-Cree First Nations population from northwestern Quebec, Canada. The condition is caused by mutations in the CIRH1A gene (also known as UTP4), which encodes a protein involved in ribosomal RNA processing and ribosome biogenesis. The disease primarily affects the hepatobiliary system, leading to progressive liver damage. NAIC typically presents in the neonatal period or early infancy with transient neonatal jaundice that may initially appear to resolve. However, the disease progresses to biliary cirrhosis during childhood, characterized by portal hypertension, hepatosplenomegaly, jaundice, pruritus (itching), and progressive liver fibrosis. The bile ducts become increasingly damaged over time, and liver function deteriorates. Laboratory findings often include elevated liver enzymes and markers of cholestasis (impaired bile flow). There is no specific curative medical therapy for NAIC. Management is primarily supportive and focuses on treating complications of cirrhosis and portal hypertension, nutritional support, and management of fat-soluble vitamin deficiencies associated with cholestasis. Liver transplantation remains the only definitive treatment for end-stage liver disease in affected individuals and has been performed successfully in some patients. Genetic counseling is recommended for families from the affected population. The condition is associated with a specific founder mutation (R565W) in the CIRH1A gene within this community.

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