Disease Definitions

The genetic disorder, prcd-PRA , causes cells in the retina at the back of the eye to degenerate and die, even though the cells seem to develop normally early in life. The “rod” cells operate in low light levels and are the first to lose normal function. Night blindness results. Then the “cone” cells gradually lose their normal function in full light situations. Most affected dogs will eventually be blind. Typically, the clinical disease is recognized first in early adolescence or early adulthood. Since age at onset of disease varies among breeds, you should read specific information for your dog. Diagnosis of retinal disease can be difficult. Conditions that seem to be prcd-PRA might instead be another disease and might not be inherited.

Prcd-PRA is inherited as a recessive trait. This means a disease gene must be inherited from each parent in order to cause disease in an offspring. Parents were either “carrier” or affected. A carrier has one disease gene and one normal gene, and is termed “heterozygous” for the disease. A normal dog has no disease gene and is termed negative – both copies of the gene are the same. And a dog with two disease genes is termed positive – both copies of the gene are abnormal. Unfortunately, at this time there is no treatment or cure for PRA. If your dog is affected, you may find it helpful to read about other owners’ experiences living with blind dogs. (suggested links: www.eyevet.org and www.blinddogs.com).

Commonly affected breeds are the American Cocker Spaniel, American Eskimo Dog, Australian Cattle Dog, Australian Shepherd, Australian Shepherd, Miniature, Australian Stumpy Tail Cattle Dog, Chesapeake Bay Retriever, Chinese Crested, Cockapoo, Dwarf Poodle, English Cocker Spaniel, Entlebucher Mountain Dog, Finnish Lapphund, Golden Retriever, Golden Doodle, Karelian Bear Dog, Kuvasz, Labradoodle, Labradoodle, Australian, Labrador Retriever, Lapponian Herder, Miniature & Toy Poodle, Norwegian Elkhound, Nova Scotia Duck Tolling Retriever, Portuguese Water Dog, Spanish Water Dog, Swedish Lapphund, Yorkshire Terrier.

 

VON WILLEBRAND DISEASE (vWD)

Von Willebrand Disease (vWD) is a common genetic bleeding disorder that can occur in dogs. In fact, it is not a single disease, but a family of related diseases of variable severity. All the different types in humans and in dogs are caused by a problem with the Von Willebrand Factor (vWF). This is a protein in blood which is necessary for proper blood coagulation, or clotting. When there is not enough of the protein in the blood, bleeding can be uncontrolled and sometimes life threatening. Symptoms can include undue bleeding of the umbilical cord at birth, extended bleeding at the time of tail docking, blood in the urine, or swelling in various body parts. Not all animals show clinical symptoms.

The disease is inherited in an autosomal recessive mode. Different types of vWD are found in different breeds of dogs.  

References: van Dongen AM, van Leeuwen M, Slappendel RJ. 2001. Canine von Willebrand's disease type 2 in German wirehair pointers in the Netherlands. Vet Rec. 148(3):80-2.

CANINE MULTIDRUG SENSITIVITY TEST (MDR1)

Some dog breeds are more sensitive to certain drugs compared to other breeds. For example, Australian Shepherds, Collies, Longhaired Whippets and other breeds are more sensitive to antiparasitic and anticancer drugs. The problem is due to a mutation in the multidrug resistance gene (MDR1). The product of MDR1 gene, P-glycoprotein, is an important component of the blood-brain barrier that is responsible for pumping many drugs out of the brain. Dogs with mutant MDR1 gene cannot remove some drugs out of the brain as normal dogs would, which may result in abnormal neurological signs. The result may be an illness requiring an extended hospital stay or even death of the dog.

In addition to its expression in the blood-brain barrier, P-glycoprotein expression occurs also in the intestinal tract, liver, and kidney. In these organs, the absence of P-glycoprotein will alter the pharmacokinetic properties of drugs identified as P-glycoprotein substrates, resulting in enhanced oral bio-availability and/or reducing drug elimination through the liver, kidney, and gut. In consequence, plasma concentrations will increase and adverse drug reactivity may occur.

Drugs that have been documented, or are strongly suspected to cause problems in dogs with MDR1 mutation:

• Acepromazine (tranquilizer)
• Butorphanol (pain control)
• Cyclosporin (immunosuppression drug)
• Digoxin (heart drug)
• Doxorubicin (anticancer drug)
• Ivermectin (antiparasitic drug)
• Loperamide (Imodium®, antidiarrheal drug)
• Moxidectin
• Vinblastine (anticancer drug)
• Vincristine (anticancer drug)

Biochemical studies have shown that mutant MDR1 gene has the potential to act on over 50 different drugs. The following drugs may potentially cause problems when given to dogs that have the mutation:

• Domperidone
• Etoposide
• Mitoxantrone
• Morphine
• Ondansetron
• Paclitaxel
• Quinidine
• Rifampicin

Multidrug sensitivity in dogs shows an autosomal recessive mode of inheritance.

Dogs affected with multidrug sensitivity typically display neurological symptoms after drug admission such as hyper salivation, ataxia, blindness, tremor, depression, coma, respiratory compromise, and death. Carriers of the mutant gene may display mild neurological manifestations. Recently, a DNA-based test for the detection of the gene responsible for multidrug sensitivity became available. Since this test directly targets the mutant gene, it is 100% accurate and provides breeders with definitive information on the genetic status of their animals. Instead of avoiding drugs as Ivermectin in known susceptible breeds, veterinarians can now determine if a dog is normal, in which case the drug can be administered, or dog is affected, in which case an alternative treatment can be given. Breeders can use this information to detect carriers and eliminate this disease from their breeding lines.

Breeds found to be effected as of late 2007 include Australian Shepherd, Collie, English Shepherd, Longhaired Whippet, McNab, Miniature Australian Shepherd, Old English Sheepdog, Shetland Sheepdog, Silken Windhound, and a variety of mixed breed dogs.

CANINE DEGENERATIVE MYELOPATHY (DM)

Degenerative myelopathy in dogs is a condition that develops as a result of nerve function loss in the spinal cord. The nerves are protected by a sheath called myelin. Myelin is also responsible for decreasing the amount of time it takes a nervous impulse to travel along the length of a nerve. In degenerative myelopathy, the myelin surrounding the nerves start to breakdown and nerves begin to degenerate in the spinal cord. Both of these processes cause changes to nervous signals as they travel up and down nerves. The cause of degenerative myelopathy is unknown. However, because of breed predispositions, it is thought that there might be a genetic component. This disease results in slowly progressive neurologic disease that that is not painful and non-reversible. Dogs affected with degenerative myelopathy ultimately lose muscle mass from the disuse of their back legs and have difficulty getting up to go outside to urinate and defecate.

Degenerative myelopathy is mostly seen in the German Shepherd Dog but can also be seen in the Welsh Corgi, Chesapeake Bay Retriever, Irish Setter, Dalmatian, Weimaraner, Great Pyrenees, Samoyed, Boxer, Briard and others. The disease can present itself as early as 5 years of age in some cases and has been seen in young German Shepherd puppies. The average age of onset is between 9 and 11 years. It is more common in males than females.