OMIA 000496-9940 : Hyperbilirubinaemia I in Ovis aries

In other species: horse , Bolivian squirrel monkey

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 143500 (trait) , 191740 (gene) , 218800 (trait)

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. An excess of bilirubin in the blood, resulting from a defect in uptake of organic anions by the liver, is called hyperbilirubinaemia I or Gilbert's syndrome. Another anion unable to be taken up by affected livers is phylloerythrin, a metabolite of chlorophyll. The resultant high blood levels of phylloerythrin result in photosensitive dermatitis. [Researched by Philippa Beard]

Species-specific description: Hyperbilirubinaemia I has been reported in Southdown sheep in New Zealand (Cunningham et al., 1942) and in an unrelated flock in California (Cornelius and Gronwall, 1965). Affected sheep are considered to be a good model for hyperbilirubinaemia I in humans. In humans, this disorder is due to a deficiency of the enzyme bilirubin glucuronosyltransferase, but such a deficiency has not yet been demonstrated in sheep. [Researched by Philippa Beard]

Clinical features: The primary clinical sign is photosensitive facial dermatitis, due to the associated defect in liver uptake of phyllorerythrin. Signs first appear at around 6-8 weeks of age, when lambs begin to eat grass. If not protected from sunlight, affected lambs develop severe dermatitis, mostly around the face and ears, which becomes infected, and eventually sloughs. Death (usually with 2-3 weeks) is a result of starvation and exhaustion (Hancock, 1950). If the lambs are protected from sunlight, they eventually die within five years, from renal failure (Cuppage et al., 1979). The cause of this renal dysfunction is not known. [Researched by Philippa Beard]

Pathology: Post-mortem reveals green and yellow discolouration of tissues, testicular atrophy, renal fibrosis, and pulmonary oedema and ascites. No gross hepatic lesions are evident. The only remarkable histopathological finding is lipofuscin accumulation in hepatocytes (McGavin, 1972). The absence of gross structural liver abnormalities helps differentiate this disorder from other forms of secondary hepatic photosensitisation, such as facial eczema. [Researched by Philippa Beard]


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.
1985 Cornelius, C.E., Rodgers, P.A., Briss, M.L., Ahlfors, C.E. :
Characterisation of a Gilbert-like syndrome in squirrel monkeys (Saimiri sciureus) Journal of Medical Primatology 14:59-74, 1985. Pubmed reference: 3999115.
1979 Cuppage, F.E., McGavin, M.D., Strafuss, A.C. :
Animal model of human disease: intrarenal obstructive uropathy with proximal actasia, cystic kidney disease. Animal Model: Gilbert's syndrome in Southdown sheep American Journal of Pathology 97:, 1979.
Cuppage, F.E., Shimamura, T., McGavin, M.D. :
Nephron obstruction in mutant Southdown sheep Veterinary Pathology 16:483-485, 1979. Pubmed reference: 452323.
1977 Filippich, L., English, P.B. :
Comparison of renal function in a congenital hyperbilirubinaemia Southdown sheep and normal sheep Research in Veterinary Science 23:204-212, 1977. Pubmed reference: 928985.
1975 Dhumeaux, D., Berthelot, P. :
Chronic hyperbilirubinaemia associated with hepatic uptake and storage impairment: a new syndrome resembling that of the mutant Southdown sheep Gastroenterology 69:988-993, 1975. Pubmed reference: 1175891.
1971 Mia, A.S., Gronwall, R.R., McGavin, M.D., Cornelius, C.E. :
Renal function defect in mutant Southdown sheep with congenital hyperbilirubinemia Proceedings of the Society for Experimental Biology and Medicine 137:1237-1241, 1971. Pubmed reference: 5138450.
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.
1969 Cornelius, C.E. :
Organic anion transport in mutant sheep with congenital hyperbilirubinemia Archives of Environmental Health 19:852-856, 1969. Pubmed reference: 5389192.

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  • Created by Frank Nicholas on 06 Sep 2005