Genetic basis of Acute Intermittent Porphyria Variant 2 - in cats is an inherited metabolic disorder of heme synthesis caused by mutations in the hydroxymethylbilane synthase (HMBS) gene. This mutation impairs the enzyme's function, essential for proper heme biosynthesis. The inheritance pattern for Variant 2 is typically autosomal dominant, meaning one copy of the defective gene can cause the disease. DNA testing is available to identify affected and carrier cats.
Pathophysiology - The HMBS enzyme deficiency reduces hydroxymethylbilane synthase activity to about half normal, disrupting the heme synthesis pathway. This leads to accumulation of porphyrin precursors such as uroporphyrin and coproporphyrin in urine and tissues. These accumulated porphyrins cause the characteristic erythrodontia (brown discoloration of teeth) and brown or red-brown urine. The porphyrins also deposit in bones and tissues, causing fluorescence under UV light. In cats, this variant can mimic congenital erythropoietic porphyria (CEP), despite different enzymatic defects. Unlike the human form, cats generally do not show acute neurovisceral symptoms.
Complications - Erythrodontia: brown or reddish-brown discoloration of the teeth, fluorescing under UV light. Red to brown urine due to porphyrin excretion. Porphyrin accumulation in bones and tissues causes fluorescence and may contribute to photosensitivity in some cases. Mild changes in blood cells possible but severe anemia is uncommon. Unlike humans with AIP, cats usually lack severe acute neurologic or abdominal episodes. Chronic accumulation may lead to secondary complications such as mild liver or skin changes, but serious systemic disease is rare.
Why This Matters to Breeders and Vets - Breeders should use genetic testing to identify affected cats and carriers to prevent breeding that produces affected offspring, especially since this is a dominant inherited condition. Veterinarians need to recognize classic signs like erythrodontia and discolored urine and confirm diagnosis with genetic or biochemical testing. Early diagnosis aids in counseling on breeding decisions and monitoring of affected cats. Although there is no cure, supportive care and avoiding triggers that might exacerbate symptoms can help affected cats live healthier lives.
Summary - Acute Intermittent Porphyria Variant 2 in cats is an autosomal dominant inherited metabolic disorder caused by mutations in the hydroxymethylbilane synthase gene, disrupting heme synthesis and leading to accumulation of porphyrins. This results in characteristic brownish teeth discoloration (erythrodontia), red or brown urine, and fluorescence of bones and tissues. The disease mimics congenital erythropoietic porphyria phenotypically but differs biochemically and genetically. Severe acute attacks typical in humans are not observed in cats. Genetic testing is available and important for breeding management. No cure exists, and care is supportive.
