Comparative Neurology Program

Lysosomal Storage Disease in the Rhodesian Ridgeback

Green fluorescent storage material in a liver biopsy from an affected dog.

A hereditary lysosomal storage disease affecting primarily the bones and liver has been identified in Rhodesian Ridgebacks in Canada, Europe and the USA. In collaboration with veterinary clinicians at Washington State University, researchers at the University of Missouri, College of Veterinary Medicine have used the latest gene discovery strategies to identify a mutation associated with the disease. A DNA test is now available to aid in the diagnosis of affected dogs and identify carriers so that responsible breeders can eliminate the disease from the breed.

What is a lysosomal storage disease?

Amino acids provide the building blocks for all the proteins in a dog's body. You can think of the amino acids like the toy plastic blocks that a child uses to build something like a toy house. Eventually, the proteins in the body get damaged or worn out and need to be replaced. Structures within the cells in our bodies called lysosomes function as the recycling centers for the cell. They can break the proteins down into their amino acids which can then be reused to build new proteins; the same way a child can take apart a plastic block house that they no longer want and use the block to build something new. A specific enzyme is required for each step in the breakdown of a complex protein into its amino acids. A hereditary deficiency in one of those enzymes sets up a road block in the breakdown of the protein. It is as if you were trying to take apart the block structure in the figure, but could not remove the red blocks. You would get stuck half-way through taking it apart and not be able to go any further. The fragments of protein then just build up in the lysosome, hence the name lysosomal storage disease. Over time, either the buildup of the partially degraded protein, or the lack of the recycled amino acids interferes with the function of the cells and progressive disease results.

   

The lysosome is the recycling center of a cell. It breaks down worn out proteins to their component amino acids which can be used to build a new protein.

 

In lysosomal storage disease, a deficiency in one step of the breakdown of the protein stops the process at that point. The remaining part of the protein that cannot be broken down gets “stored” in the lysosome and cause disease.

 

What happens to dogs with this disease?

Because lysosomal storage disease only affects the recycling of proteins, affected dogs can intially produce all the proteins that they need and thus they develop normally for a period of time. It is only when enough storage material builds up in the cells to interfere with functions that the clinical signs become apparent. Thus Rhodesian Ridgebacks with this disease did not show signs of the disease until they were 6 months to 3 years old.

Dogs with lysosomal storage disease usually develop problems in several organs since all cells have this recycling sysem. For a particular form of the disease, however, some cells are affected more than others. In Rhodesian Ridgebacks, the bones and liver appear particulary vulnerable. All the dogs presented initially with signs of lameness or back pain. Radiographs showed degenerative changes in the bones that would not be expected in such a young dog. Affects of the disease on the liver may produce abnormalities on routine blood tests. Some dogs have also shown behavior changes such as confusion and loss of house-breaking or coordination


CT scan of the spine showing abnormal bones (a) with osteopenia and fractures (b & c) compared to a vertebra from a normal dog in d. Harris et al. 2016

 

A liver biopsy may show evidence of storage material in the lysosomes. Unfortunately, there is no cure for this disease. Medication can help relieve the pain associated with the bone involvement, but affected dogs are euthanized as their quality of life deteriorates. On post-mortem examination, storage material can be found in a number of organs including the brain. A DNA test can confirm the diagnosis in a dog with signs of the disease.

A DNA test for this disease is now available

Much more common diseases such as injuries or infections of the joints or spine can cause pain. Likewise, things like drug reactions or infections can cause abnormal liver tests. If your dog is showing these signs, see your veterinarian. They will be able to look for common causes of these sypmtoms. If you or your veterinarian are concerned that you dog may have this lysosomal storage disease, please, CONTACT US. We will be able to help your veterinarian understand this disease and arrange for a DNA test that can diagnose the disease. The DNA test can also be used to identify carriers of the trait.

What if my dog is a carrier?

This disease is inherited as a recessive trait. In a recessive disease, both parents of an affected pup are carriers but do not show any symptoms of the disease. All animals have two copies of each gene, one that is inherited from the mother and one inherited from the father. A dog that has one normal gene and one gene that causes the disease is a carrier of the trait. They show no symptoms because the one good gene is enough for their bodies to develop normally, but they will pass that bad gene on to about half of their offspring. If a carrier dog is bred to another carrier, then some of the pups (25% on average) will get a bad gene from each parent. Without one good gene to carry the day, the lysosomes cannot function normally and the unlucky pup has the storage disease.

The DNA test can identify carriers of the mutation so that breeders can make wise breeding decisions. While the initial response is often to eliminate all carriers of a mutation from the breeding pool, this is not the recommended approach. If the bad gene is common in the population, eliminating all the carriers will narrow the gene pool and limit the breeding choices available. This reduces desirable genetic diversity in the breed and may inadvertently increase the incidence of other hereditary problems that may be lurking the lines that are free of the storage disease mutation. There are often highly desirable traits in the lines with a mutation that made them popular to begin with. Eliminating those lines can eliminate those desirable traits, throwing out the baby with the bathwater. The best approach is to test breeding stock and ensure that two carriers are never bred together so that no affected pups are produced. A carrier that has desirable traits can be bred to a dog who is tested clear of the mutation since no affected pups can result from such a breeding. When selecting future breeding stock, the gene status can be considered in deciding which pups to keep but does not have to be the sole factor. Over time, the prevalence of the mutation in the breed will decline while a genetic bottle-neck is avoided. The key is to ensure that carriers are never bred to each other so that no affected pups are produced.

Questions?

If you have questions about this disease or our research, please CONTACT US. While we cannot make a diagnosis or treatment recommendations, we can provide general information and direct you to a veterinary specialist who could help

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