Acute intermittent porphyria (AIP) is an inherited disorder affecting heme group synthesis, characterized by brown teeth and brown urine due to the accumulation of porphyrins. This condition is caused by mutations in the hydroxymethylbilane synthase (HMBS) gene, resulting in reduced enzyme activity in the heme group synthesis pathway.
Symptoms
Intermittent water porphyria includes clinical signs such as erythrodontia (brown teeth), brown urine and bones, which fluoresce under ultraviolet light. Affected cats may have low hemoglobin and iron levels, as well as decreased hematocrit and mean corpuscular volume. The activity of hydroxymethylbilane synthase, responsible for the synthesis of the heme group, is reduced by half and urine levels of aminolevulinic acid (ALA), porphobilinogen (PBG), uroporphyrin and coproporphyrin are elevated.
Disease Management
Disease management focuses on reducing triggers and controlling acute symptoms. It is essential to avoid stress and any agent that may induce HMB synthase enzyme activity, such as certain medications, foods or environmental changes. Administration of hemin may be necessary during acute episodes to suppress porphyrin synthesis, although its use should be carefully monitored due to possible side effects.
Genetic basis
This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease, even if they do not show symptoms, is not recommended.
Technical report
Acute intermittent porphyria (AIP) is an inherited metabolic disorder characterized by a decrease in the activity of the enzyme hydroxymethylbilane synthase (HMB-synthase), which plays a crucial role in the heme group biosynthesis pathway. This disease belongs to the group of acute hepatic porphyrias and is characterized by the accumulation of porphyrins. Biochemical and genetic studies revealed a halved HMB-synthase activity in affected cats, with mutations identified in HMB-synthase genes in each porphyric line. Here, we studied the c.250G>A variant, a G to A transition in exon 6 resulting in the substitution of alanine for threonine. Expression of this mutation produced a stable protein with approximately 35% of the activity of the wild type. Importantly, unlike the other variants described in this same gene, the c.250G>A mutation has an autosomal recessive mode of inheritance.
Most affected breeds
Domestic Shorthair
Siamese
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