Genetic basis of Acute Intermittent Porphyria - in cats is an autosomal dominant inherited disorder caused by mutations in the hydroxymethylbilane synthase (HMBS) gene. This gene encodes an enzyme essential for heme biosynthesis. Cats with AIP carry one defective copy of this gene, which results in about half-normal enzyme activity. Several different mutations have been identified in cats. Because it is dominant, affected cats will show clinical signs, and there are no carriers that do not express the disease. Genetic testing can identify affected animals and help with breeding management.
Pathophysiology - AIP is a hepatic porphyria caused by partial deficiency of hydroxymethylbilane synthase, leading to accumulation of porphyrin precursors such as 5-aminolevulinic acid and porphobilinogen. These accumulate primarily in the liver and are excreted in urine, leading to dark yellow-brown or reddish-brown urine. The excess porphyrins also deposit in teeth and bones, causing the hallmark erythrodontia (reddish-brown discoloration of teeth). Porphyrin accumulation leads to mild changes in erythrocytes but usually without severe anemia. The disease may cause neurological symptoms in humans but in cats is mainly characterized by erythrodontia and urine discoloration.
Complications - Erythrodontia: reddish-brown discoloration of teeth that fluoresce under ultraviolet light. Yellow-brown or reddish-brown urine due to porphyrin excretion. Mild changes in erythrocytes (red blood cells) may be observed. Possible secondary effects include photosensitivity (from porphyrin deposition in skin, although less commonly reported in cats). No reports of severe anemia or fatal outcomes in cats, but chronic liver-related signs could theoretically develop.
Why This Matters to Breeders and Vets - Breeders should use genetic testing to identify affected cats and avoid breeding them, as the dominant inheritance means all offspring of affected cats will be at risk. Veterinarians need to recognize the signs of AIP (especially erythrodontia and urine discoloration) and perform biochemical testing of urine porphyrins or genetic tests for definitive diagnosis. Early identification helps prevent breeding of affected cats and alerts vets to monitor for possible health complications. Providing appropriate care and advice based on diagnosis is critical to managing animal welfare.
Summary - Acute Intermittent Porphyria (Variant 1) in cats is an autosomal dominant hepatic porphyria caused by mutations in the HMBS gene, resulting in deficient hydroxymethylbilane synthase activity. It is characterized by erythrodontia (discolored teeth), dark yellow-brown urine, and mild erythrocyte changes. Unlike the human congenital erythropoietic porphyria, cats with AIP exhibit this severe tooth discoloration along with porphyrinuria. Diagnosis is confirmed by biochemical assays and genetic testing. Although severe systemic complications are uncommon, AIP is important for breeders and vets due to its hereditary nature and visible phenotypic signs.
