North American Indian childhood cirrhosis is a rare liver disorder that occurs in children. The liver malfunction causes yellowing of the skin and whites of the eyes (jaundice) in affected infants. The disorder worsens with age, progressively damaging the liver and leading to chronic, irreversible liver disease (cirrhosis) in childhood or adolescence. Unless it is treated with liver transplantation, North American Indian childhood cirrhosis typically causes life-threatening complications including liver failure.
North American Indian childhood cirrhosis has been found only in children of Ojibway-Cree descent in the Abitibi region of northwestern Quebec, Canada. At least 30 affected individuals from this population have been reported.
North American Indian childhood cirrhosis results from at least one known mutation in the UTP4 gene. This gene provides instructions for making a protein called cirhin, whose precise function is unknown. Within cells, cirhin is located in a structure called the nucleolus, which is a small region inside the nucleus where ribosomal RNA (rRNA) is produced. A chemical cousin of DNA, rRNA is a molecule that helps assemble protein building blocks (amino acids) into functioning proteins. Researchers believe that cirhin may play a role in processing rRNA. Studies also suggest that cirhin may function by interacting with other proteins.
Cirhin is found in many different types of cells, so it is unclear why the effects of North American Indian childhood cirrhosis appear to be limited to the liver. Researchers are working to determine how a UTP4 gene mutation causes the progressive liver damage characteristic of this disorder.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
Additional Information & Resources
Genetic Testing Information
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Betard C, Rasquin-Weber A, Brewer C, Drouin E, Clark S, Verner A, Darmond-Zwaig C, Fortin J, Mercier J, Chagnon P, Fujiwara TM, Morgan K, Richter A, Hudson TJ, Mitchell GA. Localization of a recessive gene for North American Indian childhood cirrhosis to chromosome region 16q22-and identification of a shared haplotype. Am J Hum Genet. 2000 Jul;67(1):222-8. doi: 10.1086/302993. Epub 2000 May 11. Citation on PubMed or Free article on PubMed Central
- Chagnon P, Michaud J, Mitchell G, Mercier J, Marion JF, Drouin E, Rasquin-Weber A, Hudson TJ, Richter A. A missense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis. Am J Hum Genet. 2002 Dec;71(6):1443-9. doi: 10.1086/344580. Epub 2002 Nov 4. Citation on PubMed or Free article on PubMed Central
- Drouin E, Russo P, Tuchweber B, Mitchell G, Rasquin-Weber A. North American Indian cirrhosis in children: a review of 30 cases. J Pediatr Gastroenterol Nutr. 2000 Oct;31(4):395-404. doi: 10.1097/00005176-200010000-00013. Citation on PubMed
- Weber AM, Tuchweber B, Yousef I, Brochu P, Turgeon C, Gabbiani G, Morin CL, Roy CC. Severe familial cholestasis in North American Indian children: a clinical model of microfilament dysfunction? Gastroenterology. 1981 Oct;81(4):653-62. Citation on PubMed