Novel Neurologic Disorder Characterized in Dalmatians

A heritable and progressive neurologic disorder in Dalmatian dogs was recently described by AKC Canine Health Foundation (CHF) funded investigator Dr. Gary Johnson of the University of Missouri. He studied DNA and clinical findings from two dogs that showed slowly progressive neurologic signs starting at 18 months of age, five relatives that had clinical signs later in life (after 11 years of age), and relatives that never showed signs of neurologic disease. Clinical signs included anxiety, pacing, cognitive decline, sleep disturbances, loss of coordination, loss of bladder and bowel control, and visual impairment. MRI scans showed generalized brain atrophy and white matter degeneration. Tissue biopsies showed a build-up of fluorescent material in the brain, optic nerve, and heart muscle cells – tell-tale signs of what is known as a lysosomal storage disease.

The genetic mutation responsible for a unique neurologic disease in Dalmatian dogs was recently identified.

What is a lysosomal storage disease?
Lysosomal storage diseases are a type of degenerative neurologic disease seen in dogs, cats, and humans. Lysosomes are known as the cellular recycling center since they help cells break down biochemical waste products. When a genetic mutation renders these lysosomal processes ineffective, waste products build up eventually choking the cell and causing cell death.

Over the past 15 years, Dr. Johnson has identified the likely genetic cause of 18 lysosomal storage diseases in at least 12 different dog breeds plus mixed breeds (www.caninegeneticdiseases.net/StorageD/SDmain.htm). CHF funding allows him to continue diagnosing and describing suspected lysosomal storage diseases as samples and data are submitted to his laboratory. Many of the mutated genes he discovers cause similar lysosomal storage diseases or other illnesses in humans. Therefore, what he learns about each disease can benefit both dogs and humans.

The lysosomal storage disease seen in the Dalmatian family had features that made it unique and different from previously described canine disorders. Genetic study revealed mutation in a gene previously not associated with lysosomal storage disease in dogs. While it’s not clear exactly how the mutated gene results in lysosomal waste build-up, the inheritance pattern shows a clear autosomal recessive pattern. The two dogs with early-onset disease had two copies of the mutated gene, while those with later-onset disease only had one copy, and healthy relatives had no copies of the mutation.

While lysosomal storage diseases are relatively rare in dogs and humans, they can be devastating for affected individuals and their families. Ongoing genetic discovery research, such as Dr. Johnson’s work, identifies the underlying mutation responsible for these disorders. Results help dog breeders make informed breeding decisions to decrease the chance of producing affected offspring. They also demonstrate the biochemical differences and similarities of these disorders between dogs and humans, allowing veterinary and human medical scientists to develop new therapies for both species more efficiently.

Learn more about CHF-funded neurology research into lysosomal storage diseases and many other neurologic conditions at akcchf.org/neurologyRPA.


Reference:
Bullock, G., Johnson, G. S., Mhlanga-Mutangadura, T., Petesch, S. C., Thompson, S., Goebbels, S., & Katz, M. L. (2022). Lysosomal Storage Disease Associated with a CNP Sequence Variant in Dalmatian Dogs. Gene, 146513. https://doi.org/10.1016/j.gene.2022.146513