Congenital erythropoietic porphyria

Congenital erythropoietic porphyria is a rare hereditary disease of cattle, pigs, cats, and humans in which defective hemoglobin formation results in production of an excess of Type I porphyrins in the nuclei of developing normoblasts. The defect in cattle is inherited as a simple autosomal recessive and is usually confined to herds in which inbreeding or close line-breeding is practiced. The condition has been recognized in the USA, Canada, Denmark, Jamaica, England, South Africa, Australia, and Argentina. This broad geographic distribution indicates that the disease likely occurs worldwide and probably affects all meat-producing animals, especially cattle, swine, and sheep.

Heterozygous animals seem to be normal, but homozygous recessive animals are affected at birth with reddish brown discoloration of the teeth, bones, and urine that persists for the life of the animal. The inherited enzymatic defect causes deficient activity of uroporphyrinogen III synthase—an essential part of porphyrin-heme biosynthesis. Uroporphyrinogen III cosynthetase is the enzyme that is deficient. The urine contains an excess of coproporphyrin I and uroporphyrin I; in affected animals, the color is amber or reddish brown. Bones, urine, and teeth (especially the deciduous teeth) fluoresce pink when irradiated with near-ultraviolet light.           Prolonged exposure to sunlight causes typical lesions of photosensitization with hyperemia, vesicle formation, and superficial necrosis of unpigmented portions of the skin. The severity of the skin lesions depends on the intensity of the solar radiation and the extent of cutaneous pigmentation occurring in specific families of animals. A normochromic, hemolytic anemia with macrocytes and microcytes and marked basophilic stippling develops. Splenomegaly eventually occurs. The texture of bones is not altered except in cases in which bones have increased fragility due to a diminished cortex. Affected animals are generally of medium to good condition unless solar injury has occurred. Some animals become progressively unthrifty unless protected from sunlight. A similar disease, bovine protoporphyria ( Cutaneous Manifestations of Multisystemic and Metabolic Defects), causes photosensitivity only in Limousin cattle and humans.

In humans, a series of porphyrias caused by defective functions of enzymes in porphyrin-heme biosynthesis have been described and grouped according to their presenting clinical signs. These vary broadly and may include severe cutaneous lesions on exposed areas of the body, acute photosensitivity reactions, serious liver damage, and acute attacks of neurologic dysfunction. In animals, the recognized diseases are commonly classified as either congenital erythropoietic porphyria, congenital erythropoietic protoporphyria, or porphyria. It is likely that all of the syndromes described in humans also occur in animals and that a broader classification could be used.

The defect in pigs and cats is extremely rare and differs from the condition in cattle in that photosensitization is not a feature. In pigs and cats, the disease is transmitted as an autosomal dominant. In pigs, even with high levels of porphyrins in the blood, photodynamic dermatitis does not occur. The disease has been reported only in Denmark and New Zealand; in cats, it has been recognized only in the USA.

Diagnosis should be based on the excretion of abnormal uroporphyrins, the brown discoloration of the teeth (which fluoresce when irradiated with near-ultraviolet light), the appearance of discolored urine, and hemolytic anemia.

The recessive genetic character is widely distributed in cattle, but the clinical condition is comparatively rare. Clinically normal heterozygotes have lower levels of uroporphyrinogen III cosynthetase than do normal animals, but laboratory identification of the carrier state is impractical due to the relatively low incidence of the disease and is not widely used. Morbidity can be controlled by keeping affected animals indoors and out of direct sunlight.