OMIA 000497-9940 : Hyperbilirubinaemia II in Ovis aries

Possibly relevant human trait(s) and/or gene(s) (MIM number): 237500

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: no

Cross-species summary: Bilirubin is an orange bile pigment produced by the breakdown of haem and reduction of biliverdinin. Bilirubin often occurs conjugated with glucuronic acid. An excess of conjugated bilirubin in the blood is called hyperbilirubnaemia II or Dubin-Johnson syndrome. As with hyperbilirubinaemia I, there is also an excess of phylloerythrin in the blood. [Researched by Philippa Beard]

Species-specific description: The first report of this disorder in sheep was by Arias et al. (1964), who presented evidence of autosomal recessive inheritance in Corriedales, which appears to be a good model for the human disorder (Cornelius et al., 1965). The biochemical/molecular cause of this disorder has not yet been determined. [Researched by Philippa Beard]

Clinical features: Clinical signs include photodynamic dermatitis predominantly around the eyes, and on the ears, due to the increased blood and liver phyllorethrin concentration. Progressive anorexia and amaciation eventually leads to death within six months (Cornelius et al., 1965). On post mortem, the livers are dark brown to black, and there is some discolouration of the kidneys. No jaundice is observed. [Researched by Philippa Beard]

Pathology: Histopathology shows brown-black granules in hepatocytes and Kupffer's cells. Hepatic architecture is nowmal. [Researched by Philippa Beard]

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
1992 Kitamura, T., Alroy, J., Gatmaitan, Z., Inoue, M., Mikami, T., Jansen, P., Arias, I.M. :
Defective Biliary Excretion of Epinephrine Metabolites in Mutant (TR-) Rats - Relation to the Pathogenesis of Black Liver in the Dubin-Johnson Syndrome and Corriedale Sheep with an Analogous Excretory Defect Hepatology 15:1154-1159, 1992. Pubmed reference: 1592353.
1979 Engelking, R., Gronwall, R. :
Bile acid clearance in sheep with hereditary hyperbilirubinaemia American Journal of Veterinary Research 40:1277-1280, 1979. Pubmed reference: 525932.
1977 Barnhart, J.L., Gronwall, R.R., Combes, B. :
Selective defect in biliary excretion of conjugated BSP compounds in mutant Corriedale sheep Gastroenterology 73:1257, 1977.
1970 Gronwall, R.R. :
Sulfobromophthalein sodium excretion and hepatic storage in Corriedale and Southdown sheep with inherited hepatic dysfunction American Journal of Veterinary Research 31:2131-2133, 1970. Pubmed reference: 5505142.
Mia, A.S., Gronwell, R.R., Cornelius, C.E. :
Unconjugated and conjugated bilirubin transport in normal and mutant Corriedale sheep with Dubin-Johnson syndrome Proceedings of the Society for Experimental Medicine 135:33-37, 1970.
1969 Cornelius, C.E. :
Organic anion transport in mutant sheep with congenital hyperbilirubinemia Archives of Environmental Health 19:852-856, 1969. Pubmed reference: 5389192.
1965 Cornelius, C.E., Arias, I.M., Osburn, B.I. :
Hepatic pigmentation with photosensitivity: a syndrome in Corriedale sheep resembling Dubin-Johnson syndrome in man Journal of the American Veterinary Medical Association 146:709-713, 1965. Pubmed reference: 14317604.
1964 Arias, I., Bernstein, L., Toffler, R., Cornelius, C., Novikoff, A.B., Essner, E. :
Black liver disease in Corriedale sheep : a new mutation affecting hepatic excretory function Journal of Clinical Investigation 43:1249-1250, 1964. Pubmed reference: 14228539. DOI: 10.1172/JCI105078.

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  • Created by Frank Nicholas on 06 Sep 2005