Genetic basis of Acute Intermittent Porphyria Variant 3 - in cats is a genetic metabolic disorder caused by mutations in the hydroxymethylbilane synthase (HMBS) gene, which encodes a critical enzyme in the heme biosynthesis pathway. The inheritance pattern is typically autosomal dominant, meaning a single mutated copy of the gene can cause the disease. Different mutations in the HMBS gene have been identified in various feline lines, causing reduced enzyme activity and resultant disease. Genetic testing for AIP Variant 3 is available for identification of affected and carrier cats.
Pathophysiology - The HMBS enzyme deficiency leads to reduced hydroxymethylbilane synthase activity, disrupting the pathway of heme synthesis and causing the accumulation of toxic porphyrin precursors such as 5-aminolevulinic acid (ALA) and porphobilinogen (PBG) as well as elevated uroporphyrin (URO) and coproporphyrin (COPRO) isomers. These accumulate in various tissues including the liver, bones, teeth, and urine. The porphyrin accumulation in teeth causes erythrodontia—a brownish discoloration of the teeth—and bones show fluorescence under UV light. Urine is often dark brown or reddish from porphyrin excretion. Though genetically and biochemically related to human AIP, this feline disease may phenotypically resemble congenital erythropoietic porphyria (CEP) due to the similar porphyrin deposits.
Complications - Erythrodontia: brownish-red discoloration of the teeth that fluoresce under ultraviolet light. Discolored urine: dark yellow to brown or red due to porphyrin excretion. Fluorescence of bones due to porphyrin accumulation. Some cats may exhibit mild hematological abnormalities but severe anemia or acute neurovisceral attacks typical of human AIP are usually absent in cats. The disease is chronic and may cause progressive tissue damage but typically lacks the acute neurological crises seen in humans.
Why This Matters to Breeders and Vets - Breeders should screen for HMBS mutations via genetic testing to prevent breeding affected cats, as AIP Variant 3 is autosomal dominant and hereditary. Veterinarians need awareness of the disease signs, including erythrodontia and discolored urine, to recommend appropriate biochemical and genetic testing. Early diagnosis enables genetic counseling and better clinical management, preventing propagation of the disease within breeding lines. Although no cure exists, supportive care and avoidance of exacerbating factors can improve welfare.
Summary - Acute Intermittent Porphyria (Variant 3) in cats is an autosomal dominant inherited heme synthesis disorder caused by mutations in the HMBS gene resulting in deficient hydroxymethylbilane synthase activity. This leads to accumulation of porphyrins causing characteristic brown teeth discoloration (erythrodontia), dark urine, and fluorescence of bones. The condition mimics aspects of congenital erythropoietic porphyria but is genetically distinct. Genetic testing aids in diagnosis and breeding decisions. There is no cure, and management is supportive.
