Genetic basis of Congenital Erythropoietic Porphyria - in cats is an autosomal recessive inherited metabolic disorder caused by mutations in the uroporphyrinogen III synthase (UROS) gene. This enzyme is critical for the heme biosynthesis pathway. Affected cats inherit two defective copies of the UROS gene (one from each parent), resulting in deficient enzyme activity. Carriers with one mutated allele typically show no clinical signs but can pass the mutation to offspring. Specific mutations identified include c.140C>T (p.S47F) and c.331G>A (p.G111S), whose combined effect causes the disease. DNA testing allows for rapid diagnosis and carrier screening to assist breeders in preventing affected kittens.
Pathophysiology - UROS is an essential enzyme that catalyzes a key step in the heme synthesis pathway, producing uroporphyrinogen III. Without sufficient UROS activity, abnormal porphyrin isomers accumulate, particularly uroporphyrin I and coproporphyrin I, which cannot be further processed, leading to toxic build-up within cells, especially in erythrocytes (red blood cells) and bone marrow. This accumulation results in the characteristic clinical signs by damaging red blood cells and other tissues. The build-up of porphyrins also causes photosensitivity and tissue fluorescence under ultraviolet (UV) light.
Complications - Erythrodontia: reddish-brown discoloration of the teeth that fluoresce under UV light, a hallmark feature. Reddish-brown urine due to porphyrin excretion. Photosensitivity causing skin lesions on sun-exposed areas. Anemia from ineffective erythropoiesis and hemolysis. Possible mild to moderate hematologic abnormalities. Progressive clinical signs in affected young cats generally result in reduced quality of life. The disease is chronic and potentially fatal without effective treatments.
Why This Matters to Breeders and Vets - Breeders should perform genetic testing to identify carriers and avoid mating two carriers, which carries a 25% risk per kitten of producing affected offspring. Responsible breeding practices can reduce disease incidence. Veterinarians must consider CEP in cats showing erythrodontia, hemolytic anemia, photosensitivity, or discolored urine. Diagnosis is supported by clinical signs, porphyrin profiling in urine and erythrocytes, and confirmation by UROS gene mutation analysis. Early identification allows for improved clinical management, guidance on environmental protection (e.g., limiting sun exposure), and breeder counseling. There is currently no cure; management is supportive and preventive.
Summary - Feline Congenital Erythropoietic Porphyria (Variant 1) is a rare autosomal recessive porphyria caused by mutations in the UROS gene, leading to deficient enzyme activity in heme synthesis. This causes accumulation of porphyrin isomers that produce hallmark features such as erythrodontia, photosensitivity, and hemolytic anemia, often appearing in young cats. Diagnostics include biochemical porphyrin analysis and genetic testing. There is no cure, so prevention through genetic screening and careful breeding is essential to control this hereditary disorder in cats.
