Congenital Erythropoietic Porphyria

 

Gene: UROS

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation 1: Substitution, UROS gene; c.140C>T (p.S47F), exon 3, cat chromosome D2.

Mutation 2: Substitution, UROS gene; c.331G>A (p.G111S), exon 6, cat chromosome D2.

Medical system: dermal

Breeds: American Curl, Cornish Rex, Domestic Cat, Donskoy, Exotic Shorthair, Kurilean Bobtail, Maine Coon, Manx, Mekong Bobtail, Norwegian Forest Cat, Persian, Ragamuffin, Ragdoll, Siberian, Singapura, Tennessee Rex, Thai, Toybob, Turkish Angora

Age of onset of symptoms: from birth and persistent throughout life.

Congenital erythropoietic porphyria is a rare hereditary disease that results in a defect in the UROS gene that is responsible for the production of the protein uroporphyrin cosynthetase.  This enzyme is essential for the biosynthetic reaction of the heme nucleus contained in hemoglobin. In the absence of the enzyme, porphyrins are accumulated in the red blood cells and can subsequently be released and accumulate in tissues.   This will cause a brown discoloration of the skin, teeth, bones, and urine that is dark red.  The discolored teeth fluoresce pink with ultraviolet light.  There is no treatment for the condition, but some preventive measures are advised, such as reduced exposure to sunlight and non-breeding of affected animals or carriers of the mutation.  A DNA test for the mutation is available.

 

References:

OMIA link: [1175-9685]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804. [pubmed/35709088]

Clavero S, Ahuja Y, Bishop DF, et al. (2013) Diagnosis of feline acute intermittent porphyria presenting with erythrodontia requires molecular analyses. Vet J. 198(3):720-2. [pubmed/24239138]

Clavero S, Bishop DF, Giger U, et al. (2010) Feline congenital erythropoietic porphyria: Two homozygous UROS missense mutations cause the enzyme deficiency and porphyrin accumulation. Mol Med 16:381-388, 2010. [pubmed/20485863]

 

Contributed by: Aylin Victoria Abanto Roncal and Emmanuelle Jetté, Class of 2027, Faculté de médecine vétérinaire, Université de Montréal.   (Translation DWS).