Genetic basis of Acute Intermittent Porphyria Variant 6 - in cats is an autosomal dominant inherited disorder caused by mutations in the hydroxymethylbilane synthase (HMBS) gene. This means that only one copy of the mutated gene is required for the cat to be affected. The specific mutation in Variant 6 leads to deficient enzyme activity critical for normal heme biosynthesis. Genetic testing exists to identify affected cats and carriers, supporting breeding decisions to prevent disease propagation.
Pathophysiology - The mutation causes reduced activity of hydroxymethylbilane synthase, an essential enzyme in the heme biosynthesis pathway. Reduced enzyme function leads to accumulation of porphyrin precursors such as 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), and excess uroporphyrin and coproporphyrin in urine and tissues. These accumulated porphyrins cause characteristic symptoms including brown or reddish discoloration of teeth (erythrodontia), dark yellow-brown urine, and fluorescence of bones under UV light. Like other AIP variants in cats, Variant 6 often phenotypically resembles congenital erythropoietic porphyria but is genetically distinct.
Complications - Erythrodontia: brown/reddish teeth discoloration with pink fluorescence under ultraviolet light. Dark yellow to brownish urine from porphyrin excretion. Fluorescent bones due to porphyrin deposition. Mild hematological changes may be present, but acute neurovisceral attacks typical in humans are usually absent in cats. Chronic porphyrin accumulation may cause progressive tissue pigmentation but generally lacks severe systemic illness. The condition is lifelong and requires management but is not typically fatal.
Why This Matters to Breeders and Vets - Breeders: Autosomal dominant inheritance means every offspring of an affected cat has a 50% chance of inheriting the mutation. Genetic testing is critical to identify affected cats and prevent breeding that produces affected kittens. Responsible breeding reduces disease incidence. Veterinarians: Recognition of clinical signs such as erythrodontia and abnormal urine color should prompt genetic and biochemical testing for diagnosis. Early diagnosis aids in genetic counseling and management. Though incurable, diagnosing AIP Variant 6 improves animal welfare through client education and mitigations.
Summary - Acute Intermittent Porphyria (Variant 6) in cats is an autosomal dominant inherited metabolic disorder caused by HMBS gene mutations leading to deficient hydroxymethylbilane synthase activity. This disrupts heme synthesis causing accumulation of porphyrins responsible for characteristic erythrodontia, colored urine, and fluorescent bones. The disease is visually and biochemically similar to other variants and mimics aspects of congenital erythropoietic porphyria. Genetic testing is available and essential for diagnosis and breeding management. There is no cure, but early detection and supportive care improve quality of life.
