Present at birth
For autosomal recessive disorders, cats with two copies of the variant are at risk of developing the condition. Cats with one copy of the variant are considered carriers and are usually not at risk of developing the disorder. However, carriers of some complex variants grouped in this category may be associated with a low risk of developing the disorder. Individuals with one or two copies may pass the disorder-associated variant to their kittens if bred.
At risk cats are highly likely to show signs of this disease in their lifetime.
Partner with your veterinarian to make a plan regarding your cat’s well-being, including any insights provided through genetic testing. If your pet is at risk or is showing signs of this disorder, then the first step is to speak with your veterinarian.
Cats with this variant are asymptomatic until they are exposed to a medication that uses the pump that is rendered defective by the mutation in the MDR1 (also called ABCB1) gene. Drugs known to use this P-glycoprotein pump are macrocyclic lactones including eprinomectin-containing products labeled for use in cats (antiparasitic drugs), loperamide (antidiarrheal), erythromycin (antibiotic), acepromazine (tranquilizer), butorphanol (opioid), and certain drugs used in cancer treatment (vincristine, vinblastine, and doxorubicin). When these medications are administered, they accumulate in the brain which results in the adverse reactions. Typical symptoms involve generalized neurologic dysfunction including mydriasis, dyspnea, tremors, jumpiness, ataxia, and seizures. Neurologic symptoms can be quite severe in affected cats and should not be left untreated. However, with appropriate supportive care by a veterinarian, affected cats may be able to fully recover.
Research studies have shown that cats with two copies of the MDR1 Medication Sensitivity variant are affected by this condition and have suggested, in theory, that cats with one copy of the MDR1 Medication Sensitivity variant may also be affected if treated with higher doses of drugs known to use the P-glycoprotein pump. Therefore, the current recommendation when treating cats with this variant is to adhere to similar precautions recommended for dogs with this variant. It is important to be aware of medications which may result in an adverse reaction. These include: Acepromazine, Butorphanol, Doxorubicin, Doramectin, Emodepside, Eprinomectin, Erythromycin, Ivermectin, Loperamide, Milbemycin, Moxidectin, Paclitaxel, Rifampin, Selamectin, Vinblastine, Vincristine. It is best to explore alternative medications that will not use the P-glycoprotein pump. In the case of Eprinomectin, affected cats can experience adverse reactions even when treated with eprinomectin-containing products labeled for use in cats and administered according to label instructions. Therefore, affected cats should not be treated with any eprinomectin-containing products. While further research is needed on the safety of treating affected cats with other macrocyclic lactone-containing products, a recent study of eprinomectin-containing products in affected cats indicates that caution is advised when using this class of drug in cats with the MDR1 Medication Sensitivity variant. Unfortunately, there is no antidote when treating cats with macrocyclic lactone toxicosis due to this condition. If the product was administered topically, the cat should be bathed to prevent further absorption of the product and then treatment consists of providing necessary supportive care. With appropriate supportive care, affected cats may be able to fully recover from the adverse reaction.
There are many responsibilities to consider when breeding cats. Regardless of test results it is important that your cat is in good general health and that you are in a position to care for the kittens if new responsible owners are not found. For first time or novice breeders, advice can be found at most cat registry websites.
Further research is needed to determine if cats with one copy of the variant may be at risk for showing clinical signs. Breeding cats with one or two copies of the MDR1 Medication Sensitivity variant should be approached with caution at this time. If a cat with one copy of the MDR1 Medication Sensitivity variant is bred with a clear cat with no copies of the MDR1 Medication Sensitivity variant, about half of the kittens will have one copy and half will have no copies of the MDR1 Medication Sensitivity variant. If a cat with two copies of the MDR1 Medication Sensitivity variant is bred with a clear cat with no copies of the MDR1 Medication Sensitivity variant, the resulting kittens will all have one copy of the MDR1 Medication Sensitivity variant. If litters are expected to contain kittens with one copy of the MDR1 Medication Sensitivity variant, the kittens should be DNA tested as they may show signs of sensitivity to some medications. Carrier to carrier matings are not advised as the resulting litter may contain kittens with two copies of the MDR1 Medication Sensitivity variant, which is known to cause medication sensitivity. Please note: It is possible that disease signs similar to the ones caused by the MDR1 Medication Sensitivity variant could develop due to a different genetic or clinical cause.
All coordinates reference FelCat9.0
Mealey, K. L., & Burke, N. S. (2015). Identification of a nonsense mutation in feline ABCB1. Journal of Veterinary Pharmacology and Therapeutics, 38(5), 429–433. View the article
Mealey, K. L., Burke, N. S. Rebecca, & Connors, R. L. (2021). Role of an ABCB1 1930_1931del TC gene mutation in a temporal cluster of macrocyclic lactone-induced neurologic toxicosis in cats associated with products labelled for companion animal use. J Am Vet Med Assoc . 2021 Jul 1;259(1):72-76 View the article